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Cited by 170Vitamin D Research StudiesDermatology and Skin DiseasesSteroid Chemistry and Biochemistry

The role of CYP11A1 in the production of vitamin D metabolites and their role in the regulation of epidermal functions

Open access
Slominski, Andrzej T., Kim, Tae-Kang, Li, Wei, Yi, Ae-Kyung, Postlethwaite, Arnold, Tuckey, Robert C.·2014·The Journal of Steroid Biochemistry and Molecular Biology
DOI 10.1016/j.jsbmb.2013.10.012PMC PMC4002668
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Abstract

Research over the last decade has revealed that CYP11A1 can hydroxylate the side chain of vitamin D3 at carbons 17, 20, 22 and 23 to produce at least 10 metabolites, with 20(OH)D3, 20,23(OH)2D3, 20,22(OH)2D3, 17,20(OH)2D3 and 17,20,23(OH)3D3 being the main products. However, CYP11A1 does not act on 25(OH)D3. The placenta, adrenal glands and epidermal keratinocytes have been shown to metabolize vitamin D3 via this CYP11A1-mediated pathway that is modified by the activity of CYP27B1, with 20(OH)D3 (the major metabolite), 20,23(OH)2D3, 1,20(OH)2D3, 1,20,23(OH)3D3 and 17,20,23(OH)3D3 being detected, defining these secosteroids as endogenous regulators/natural products. This is supported by the detection of a mono-hydroxyvitamin D3 with the retention time of 20(OH)D3 in human serum. In new work presented here we demonstrate that the CYP11A1-initiated pathways also occurs in Caco-2 colon cells. Our previous studies show that 20(OH)D3 and 20,23(OH)2D3 are non-calcemic at pharmacological doses, dependent in part on their lack of a C1α hydroxyl group. In epidermal keratinocytes, 20(OH)D3, 20(OH)D2 and 20,23(OH)2D3 inhibited cell proliferation, stimulated differentiation and inhibited NF-κB activity with potencies comparable to 1,25(OH)2D3, acting as partial agonists on the VDR. 22(OH)D3 and 20,22(OH)2D3, as well as secosteroids with a short or no side chain, showed antiproliferative and prodifferentiation effects, however, with lower potency than 20(OH)D3 and 20,23(OH)2D3. The CYP11A1-derived secosteroids also inhibited melanocyte proliferation while having no effect on melano-genesis, and showed anti-melanoma activities in terms of inhibiting proliferation and the ability to grow in soft agar. Furthermore, 20(OH)D3 and 20,23(OH)2D3 showed anti-fibrosing effects in vitro, and also in vivo for the former. New data presented here shows that 20(OH)D3 inhibits LPS-induced production of TNFα in the J774 line, TNFα and IL-6 in peritoneal macrophages and suppresses the production of proinflammatory Th1/Th17-related cytokines, while promoting the production of the anti-inflammatory cytokine IL-10 in vivo. In summary, CYP11A1 initiates new pathways of vitamin D metabolism in a range of tissues and products could have important physiological roles at the local or systemic level. In the skin, CYP11A1-derived secosteroids could serve both as endogenous regulators of skin functions and as excellent candidates for treatment of hyperproliferative and inflammatory skin disorders, and skin cancer. This article is part of a Special Issue entitled ‘16th Vitamin D Workshop’.

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Crossref · 10.1016/j.jsbmb.2013.10.012

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  • Findingown data

    20(OH)D3 inhibits LPS-induced TNFα production in the J774 cell line.

    “New data presented here shows that 20(OH)D3 inhibits LPS-induced production of TNFα in the J774 line”
    Quote in the paperSubstantial claim
  • Findingown data

    CYP11A1-initiated pathways occur in Caco-2 colon cells.

    “In new work presented here we demonstrate that the CYP11A1-initiated pathways also occurs in Caco-2 colon cells.”
    Quote in the paperSubstantial claim
  • Findingown data

    20(OH)D3 inhibits LPS-induced TNFα and IL-6 production in peritoneal macrophages.

    “TNFα and IL-6 in peritoneal macrophages”
    Quote in the paperSubstantial claim
  • Findingcitation

    In modeled VDR complexes, these secosteroids orient their side chains toward the receptor surface and bury the secocholesta head deep in the pocket bottom.

    “These secosteroids posed the side chains toward the surface of VDR and buried the secocholesta head deeply inside the pocket bottom [73].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [73] Kim TK Wang J Janjetovic Z Chen J Tuckey RC Nguyen MN Tang EK Miller D Li W Slominski AT Correlation between secosteroid-induced vitamin D receptor activity in melanoma cells and computer-modeled receptor binding strength Mol. Cell. Endocrinol 2012 361 1–2 143 152 22546549 PMC3409337 source

      Not checked in the free run.

  • Findingown data

    In peritoneal macrophages from DBA1 mice with collagen-induced arthritis, 20(OH)D3 significantly inhibits LPS-induced production of TNFα and IL-6.

    “in peritoneal macrophages isolated from DBA1 mice with collagen-induced arthritis (CIA), 20(OH)D3 significantly inhibited LPS-induced production of proinflammatory cytokines TNFα and IL-6”
    Quote in the paperSubstantial claim
  • May combine two claims. 60
  • Classified as probably not a substantial claim. 1

  • May combine two claims.

    Findingown data

    20(OH)D3 suppresses production of proinflammatory Th1/Th17-related cytokines and promotes production of the anti-inflammatory cytokine IL-10 in vivo.

    “suppresses the production of proinflammatory Th1/Th17-related cytokines, while promoting the production of the anti-inflammatory cytokine IL-10 in vivo”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Caco-2 cells metabolize exogenous vitamin D3 to 20(OH)D3 as the predominant metabolite, with lesser production of 22(OH)D3 and 25(OH)D3, and subsequent metabolism to 20,23(OH)2D3, 1,20(OH)2D3, and 1,25(OH)2D3.

    “LC/MS analyses have demonstrated that Caco-2 cells can metabolize exogenous vitamin D3 to 20(OH)D3 as the predominant metabolite, with lesser production of 22(OH)D3 and 25(OH)D3, and subsequent metabolism to 20,23(OH)2D3, 1,20(OH)2D3 and 1,25(OH)2D3.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    When lymphoid cells were stimulated with antigen only, 1,25(OH)D3 and 20(OH)D3 suppressed IL-2 production; when stimulated with anti-CD3 antibody, all analogs suppressed IL-2 production.

    “when lymphoid cells were stimulated with antigen only, 1,25(OH)D3 and 20(OH)D3 suppressed IL-2 production, however, when lymphoid cells were stimulated with anti-CD3 antibody (Experiment 2), all analogs suppressed IL-2 production”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The data demonstrate potent suppression of the Th1 cytokine IFNY by antigen or anti-CD3 stimulated lymphoid cells, and marked suppression of the Th17 cytokine IL-17 by anti-CD3 stimulated lymphoid cells.

    “These data demonstrate that there is a potent suppression of the production of Th1 cytokine, IFNY, by either specific antigen or anti-CD3 stimulated lymphoid cells, and marked suppression of the Th17 cytokine, IL-17, by anti-CD3 stimulated lymphoid cells.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    20(OH)D3 has a docking score of -12.86 and forms only two hydrogen bonds through its C3 hydroxyl; no hydrogen bond is predicted from its 20-hydroxy group.

    “20(OH)D3 only displays two hydrogen bonding interactions to the VDR which involve the C3 hydroxyl group, giving a docking score of −12.86 (Fig. 5B). No hydrogen bonding interactions were predicted to form from the 20-hydroxy group.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Vitamin D3 hydroxy-derivatives with a full-length side chain and pD secosteroids with a shortened side chain stimulated VDR translocation and inhibited proliferation, with the full-length derivatives being more potent.

    “Vitamin D3 hydroxy-derivatives with a full-length side chain and hydroxy-secosteroids with a shortened side chain (pD) stimulated VDR translocation and inhibited proliferation, however, with the former being more potent than pDs.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingnone given

    The metabolites display high biological potencies with effects that depend on cell lineage.

    “The metabolites display high biological potencies with specific effects dependent on cell lineage, and show a lack of calcemic or other toxic effects at pharmacological doses far above the toxicity levels of 25(OH)D3 or 1,25(OH)2D3.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    20(OH)D3 at doses up to 3.0 μg/kg had no calcemic activity in rats, while 1,25(OH)2D3 at the same dose raised calcium to 16.0 ± 1.2 mg/dL.

    “20(OH)D3 at a doses as high as 3.0 μg/kg had no calcemic activity in rats whereas 1,25(OH)2D3 at the same dose raised calcium to 16.0 ± 1.2 mg/dL [84].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [84] Slominski AT Janjetovic Z Fuller BE Zmijewski MA Tuckey RC Nguyen MN Sweatman T Li W Zjawiony J Miller D Chen TC Lozanski G Holick MF Products of vitamin D3 or 7-dehydrocholesterol metabolism by cytochrome P450scc show anti-leukemia effects, having low or absent calcemic activity PLoS One 2010 5 3 e9907 20360850 PMC2845617 source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    1,25(OH)2D3 has a docking score of -16.99 and forms six hydrogen bonds with Ser237, Arg274, Ser278, Phe143, His305, and His397.

    “As shown in Fig. 5A, the native ligand of the VDR, 1,25(OH)2D3, has a docking score of −16.99 (more negative scores predict more favorable binding to the VDR). It forms six hydrogen bonding interactions to Ser237, Arg274, Ser278, Phe143, His305 and His397.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    20(OH)D3 significantly inhibits (>3 times) LPS-induced TNFα production in the J774 line, which expresses VDR, but not in RAW264.7 cells where VDR expression is very low.

    “20(OH)D3 significantly inhibits (>3 times) LPS-induced TNFα production in the J774 line which expresses the VDR, but not in the RAW264.7 cell line where VDR expression is very low”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Adding a 1α-hydroxy group to 20(OH)D3 is predicted to improve VDR binding, giving four hydrogen bonds and a docking score of 14.75 as reported.

    “The addition of 1α-hydroxy group is predicted to improve its binding to the VDR with a total of four hydrogen bonds (Fig. 5C, docking score 14.75).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Repeated molecular modeling with the XP glide module confirmed earlier analyses, produced more precise scores, and established a theoretical correlation with activity for newly characterized CYP11A1-derived hydroxy-derivatives.

    “These calculations, while confirming previous analyses, provided more precise numbers and importantly established a theoretical correlation with activity for the new CYP11A1-derived hydroxy-dervatives that were not analyzed previously (see Section 5).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [89] Friesner RA Murphy RB Repasky MP Frye LL Greenwood JR Halgren TA Sanschagrin PC Mainz DT Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes J. Med. Chem 2006 49 21 6177 6196 17034125

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    Antigen stimulation of lymphoid cells in the presence of 1,25(OH)D3 or 20(OH)D3 increased production of IL-4 and IL-10, while anti-CD3 stimulation showed a trend to suppress IL-4 and IL-10 production that did not reach statistical significance (p > 0.05).

    “Antigen stimulation of lymphoid cells in the presence of 1,25(OH)D3 or 20(OH)D3 increased production of anti-inflammatory cytokines IL-4 and IL-10 (Experiment 1) while all analogs showed a trend to suppress IL-4 and IL-10 production by anti-CD3 stimulated lymphoid cells (Experiment 2), but not reaching statistical significance (p > 0.05).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    20(OH)D3 markedly suppresses arthritis in the DBA/1 Lac J CIA model of rheumatoid arthritis, associated with downregulation of Th1 and Th17 cytokine production.

    “the new data in Table 2 shows that 20(OH)D3 markedly suppresses arthritis in the DBA/1 Lac J CIA model of rheumatoid arthritis (RA) that is associated with down regulation of Th1 and Th17 cytokine production”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The collagen-induced arthritis model in DBA/1 Lac J mice is a valid model of human rheumatoid arthritis.

  • May combine two claims.

    Premisecitation

    20(OH)D3 and 20,23(OH)2D3 have anti-fibrosing effects in vitro, and 20(OH)D3 also has such effects in vivo.

    “Furthermore, 20(OH)D3 and 20,23(OH)2D3 showed anti-fibrosing effects in vitro, and also in vivo for the former.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [86] Slominski A Janjetovic Z Tuckey RC Nguyen MN Bhattacharya KG Wang J Li W Jiao Y Gu W Brown M Postlethwaite AE 20S-hydroxyvitamin D3, noncalcemic product of CYP11A1 action on vitamin D3, exhibits potent antifibrogenic activity in vivo J. Clin. Endocrin. Metab 2013 98 2 E298 E303 PMC3565109 23295467 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    CYP11A1 hydroxylates the vitamin D3 side chain at carbons 17, 20, 22, and 23, yielding at least ten metabolites.

    “CYP11A1 can hydroxylate the side chain of vitamin D3 at carbons 17, 20, 22 and 23 to produce at least 10 metabolites”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [42] Guryev O Carvalho RA Usanov S Gilep A Estabrook RW A pathway for the metabolism of vitamin D3: unique hydroxylated metabolites formed during catalysis with cytochrome P450scc (CYP11A1) Proc. Nat. Acad. Sci. USA 2003 100 25 14754 14759 14657394 PMC299797

      Not checked in the free run.

    • cites [46] Slominski A Semak I Zjawiony J Wortsman J Li W Szczesniewski A Tuckey RC The cytochrome P450scc system opens an alternate pathway of vitamin D3 metabolism FEBS J 2005 272 16 4080 4090 16098191 PMC2234577 source

      Not checked in the free run.

    • cites [47] Tuckey RC Li W Zjawiony JK Zmijewski MA Nguyen MN Sweatman T Miller D Slominski A Pathways and products for the metabolism of vitamin D3 by cytochrome P450scc FEBS J 2008 275 10 2585 2596 18410379 PMC2562691 source

      Not checked in the free run.

    • cites [48] Tuckey RC Li W Shehabi HZ Janjetovic Z Nguyen MN Kim TK Chen J Howell DE Benson HA Sweatman T Baldisseri DM Slominski A Production of 22-hydroxy metabolites of vitamin D3 by cytochrome p450scc (CYP11A1) and analysis of their biological activities on skin cells Drug Metab. Dispos. Biol. Fate Chem 2011 39 9 1577 1588 21677063 PMC3164270 source

      Not checked in the free run.

  • May combine two claims.

    Premiseown data

    CYP11A1-derived secosteroids inhibit melanocyte proliferation without affecting melanogenesis, and show anti-melanoma activities including inhibition of proliferation and soft agar growth.

    “The CYP11A1-derived secosteroids also inhibited melanocyte proliferation while having no effect on melano-genesis, and showed anti-melanoma activities in terms of inhibiting proliferation and the ability to grow in soft agar.”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [59] Slominski AT Kim TK Janjetovic Z Tuckey RC Bieniek R Yue J Li W Chen J Nguyen MN Tang EK Miller D Chen TC Holick M 20-Hydroxyvitamin D2 is a noncalcemic analog of vitamin D with potent antiproliferative and prodifferentiation activities in normal and malignant cells Am. J. Physiol. Cell Physiol 2011 300 3 C526 C541 21160030 PMC3063966 source

      Not checked in the free run.

    • cites [63] Slominski A Kim TK Zmijewski MA Janjetovic Z Li W Chen J Kusniatsova EI Semak I Postlethwaite A Miller D Zjawiony J Tuckey RC Novel vitamin D photoproducts and their precursors in the skin Dermatoendocrinology 2013 5 1 7 19 PMC3897599 24494038 source

      Not checked in the free run.

    • cites [71] Slominski A Li W Zbytek B Tuckey RC Zjawiony J Nguyen MN Janjetovic Z Zmijewski M Sweatman T Miller D Chen J Postlethwaite A Enzymatic production or chemical synthesis and uses for 5,7-dienes and UVB conversion products thereof 2011 US2011/0118228A1

      Not checked in the free run.

    • cites [77] Janjetovic Z Brozyna AA Tuckey RC Kim TK Nguyen MN Jozwicki W Pfeffer SR Pfeffer LM Slominski AT High basal NF-kappaB activity in nonpigmented melanoma cells is associated with an enhanced sensitivity to vitamin D3 derivatives Br. J. Cancer 2011 105 12 1874 1884 22095230 PMC3251881 source

      Not checked in the free run.

    • cites [78] Slominski AT Janjetovic Z Kim TK Wright AC Grese LN Riney SJ Nguyen MN Tuckey RC Novel vitamin D hydroxyderivatives inhibit melanoma growth and show differential effects on normal melanocytes Anticancer Res 2012 32 9 3733 3742 22993313 PMC3458587

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    22(OH)D3 and 20,22(OH)2D3, as well as secosteroids with a short or no side chain, have antiproliferative and prodifferentiation effects but lower potency than 20(OH)D3 and 20,23(OH)2D3.

    “22(OH)D3 and 20,22(OH)2D3, as well as secosteroids with a short or no side chain, showed antiproliferative and prodifferentiation effects, however, with lower potency than 20(OH)D3 and 20,23(OH)2D3.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [48] Tuckey RC Li W Shehabi HZ Janjetovic Z Nguyen MN Kim TK Chen J Howell DE Benson HA Sweatman T Baldisseri DM Slominski A Production of 22-hydroxy metabolites of vitamin D3 by cytochrome p450scc (CYP11A1) and analysis of their biological activities on skin cells Drug Metab. Dispos. Biol. Fate Chem 2011 39 9 1577 1588 21677063 PMC3164270 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In epidermal keratinocytes, 20(OH)D3, 20(OH)D2, and 20,23(OH)2D3 inhibit proliferation, stimulate differentiation, and inhibit NF-κB activity with potency comparable to 1,25(OH)2D3, acting as partial VDR agonists.

    “In epidermal keratinocytes, 20(OH)D3, 20(OH)D2 and 20,23(OH)2D3 inhibited cell proliferation, stimulated differentiation and inhibited NF-κB activity with potencies comparable to 1,25(OH)2D3, acting as partial agonists on the VDR.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [68] Zbytek B Janjetovic Z Tuckey RC Zmijewski MA Sweatman TW Jones E Nguyen MN Slominski AT 20-Hydroxyvitamin D3, a product of vitamin D3 hydroxylation by cytochrome P450scc, stimulates keratinocyte differentiation J. Invest. Dermatol 2008 128 9 2271 2280 18368131 PMC2574837 source

      Not checked in the free run.

    • cites [69] Janjetovic Z Tuckey RC Nguyen MN Thorpe EM Jr. Slominski AT 20, 23-dihydroxyvitamin D3, novel P450scc product, stimulates differentiation and inhibits proliferation and NF-kappaB activity in human keratinocytes J. Cell. Physiol 2010 223 1 36 48 20020487 PMC2814891 source

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    • cites [70] Janjetovic Z Zmijewski MA Tuckey RC DeLeon DA Nguyen MN Pfeffer LM Slominski AT 20-Hydroxycholecalciferol, product of vitamin D3 hydroxylation by P450scc, decreases NF-kappaB activity by increasing IkappaB alpha levels in human keratinocytes PLoS One 2009 4 6 e5988 19543524 PMC2694402 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    In non-classical steroidogenic tissues, CYP11A1 expression is relatively low, making major systemic effects unlikely but local effects highly probable.

    “The expression of CYP11A1 in these non-classical steroidogenic tissues/cells, or their malignant counterparts, is relatively low and consequently the products are unlikely to have major systemic effects. However, a range of local effects is highly probable”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [20] Taves MD Gomez-Sanchez CE Soma KK Extra-adrenal glucocorticoids and mineralocorticoids: evidence for local synthesis, regulation, and function Am. J. Physiol. Endocrinol. Metab 2011 301 1 E11 E24 21540450 PMC3275156 source

      Not checked in the free run.

    • cites [21] Slominski A Zbytek B Nikolakis G Manna PR Skobowiat C Zmijewski M Li W Janjetovic Z Postlethwaite A Zouboulis CC Tuckey RC Steroidogenesis in the skin: Implications for local immune functions J. Steroid Biochem. Mol. Biol 2013 137 107 123 23435015 PMC3674137 source

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    Ergosterol can be metabolized by CYP11A1 but without side chain cleavage.

    “Ergosterol, another Δ7 sterol that is the major membrane sterol in fungi, can also be metabolized by CYP11A1 but unlike 7DHC, no cleavage of the side chain occurs”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [43] Slominski A Semak I Zjawiony J Wortsman J Gandy MN Li J Zbytek B Li W Tuckey RC Enzymatic metabolism of ergosterol by cytochrome p450scc to biologically active 17alpha, 24-dihydroxyergosterol Chem. Biol 2005 12 8 931 939 16125105 source

      Not checked in the free run.

    • cites [44] Tuckey RC Nguyen MN Chen J Slominski AT Baldisseri DM Tieu EW Zjawiony JK Li W Human cytochrome P450scc (CYP11A1) catalyzes epoxide formation with ergosterol Drug Metab. Dispos. Biol. Fate Chem 2012 40 3 436 444 22106170 PMC3286270 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    In skin, CYP11A1-derived secosteroids could act as endogenous regulators of skin functions and as treatment candidates for hyperproliferative and inflammatory skin disorders and skin cancer.

    “In the skin, CYP11A1-derived secosteroids could serve both as endogenous regulators of skin functions and as excellent candidates for treatment of hyperproliferative and inflammatory skin disorders, and skin cancer.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Effects of CYP11A1-derived secosteroids observed in cell culture and mouse models are predictive of therapeutic effects in humans.

  • May combine two claims.

    Premisecitation

    CYP11A1 only hydroxylates the vitamin D3 side chain and cannot cleave it.

    “CYP11A1 only catalyses hydroxylation of the side chain of vitamin D3 and cannot cleave it”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [42] Guryev O Carvalho RA Usanov S Gilep A Estabrook RW A pathway for the metabolism of vitamin D3: unique hydroxylated metabolites formed during catalysis with cytochrome P450scc (CYP11A1) Proc. Nat. Acad. Sci. USA 2003 100 25 14754 14759 14657394 PMC299797

      Not checked in the free run.

    • cites [46] Slominski A Semak I Zjawiony J Wortsman J Li W Szczesniewski A Tuckey RC The cytochrome P450scc system opens an alternate pathway of vitamin D3 metabolism FEBS J 2005 272 16 4080 4090 16098191 PMC2234577 source

      Not checked in the free run.

    • cites [47] Tuckey RC Li W Zjawiony JK Zmijewski MA Nguyen MN Sweatman T Miller D Slominski A Pathways and products for the metabolism of vitamin D3 by cytochrome P450scc FEBS J 2008 275 10 2585 2596 18410379 PMC2562691 source

      Not checked in the free run.

    • cites [48] Tuckey RC Li W Shehabi HZ Janjetovic Z Nguyen MN Kim TK Chen J Howell DE Benson HA Sweatman T Baldisseri DM Slominski A Production of 22-hydroxy metabolites of vitamin D3 by cytochrome p450scc (CYP11A1) and analysis of their biological activities on skin cells Drug Metab. Dispos. Biol. Fate Chem 2011 39 9 1577 1588 21677063 PMC3164270 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Human CYP11A1 catalyzes epoxidation of the C22-C23 double bond and hydroxylation at C20 of ergosterol, generating 20-hydroxy-22,23-epoxy-22,23-dihydroergosterol as a major metabolite.

    “Human CYP11A1 was found to catalyze epoxidation of the C22 C23 double bond as well as hydroxylation of the ergosterol side chain at C20, generating 20-hydroxy-22,23-epoxy-22,23-dihydroergosterol as a major metabolite”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [44] Tuckey RC Nguyen MN Chen J Slominski AT Baldisseri DM Tieu EW Zjawiony JK Li W Human cytochrome P450scc (CYP11A1) catalyzes epoxide formation with ergosterol Drug Metab. Dispos. Biol. Fate Chem 2012 40 3 436 444 22106170 PMC3286270 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The favored hydroxylation site on vitamin D3 by CYP11A1 is C20 rather than C22, with 20(OH)D3 as the major metabolite.

    “The favored site of hydroxylation is at C20 rather than C22, with 20(OH)D3 being the major metabolite”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [42] Guryev O Carvalho RA Usanov S Gilep A Estabrook RW A pathway for the metabolism of vitamin D3: unique hydroxylated metabolites formed during catalysis with cytochrome P450scc (CYP11A1) Proc. Nat. Acad. Sci. USA 2003 100 25 14754 14759 14657394 PMC299797

      Not checked in the free run.

    • cites [46] Slominski A Semak I Zjawiony J Wortsman J Li W Szczesniewski A Tuckey RC The cytochrome P450scc system opens an alternate pathway of vitamin D3 metabolism FEBS J 2005 272 16 4080 4090 16098191 PMC2234577 source

      Not checked in the free run.

    • cites [47] Tuckey RC Li W Zjawiony JK Zmijewski MA Nguyen MN Sweatman T Miller D Slominski A Pathways and products for the metabolism of vitamin D3 by cytochrome P450scc FEBS J 2008 275 10 2585 2596 18410379 PMC2562691 source

      Not checked in the free run.

    • cites [48] Tuckey RC Li W Shehabi HZ Janjetovic Z Nguyen MN Kim TK Chen J Howell DE Benson HA Sweatman T Baldisseri DM Slominski A Production of 22-hydroxy metabolites of vitamin D3 by cytochrome p450scc (CYP11A1) and analysis of their biological activities on skin cells Drug Metab. Dispos. Biol. Fate Chem 2011 39 9 1577 1588 21677063 PMC3164270 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    CYP11A1 protein and enzymatic activity, adrenodoxin, adrenodoxin reductase, StAR, and STARD3 are detected in whole skin and skin cells.

    “expression of CYP11A1 protein and its corresponding enzymatic activity, as well as adrenodoxin, adrenodoxin reductase, the Steroidogenic Acute Regulatory protein (StAR or STARD1) and another member of the START domain family, STARD3 (also known as MLN64), were detected in whole skin and skin cells”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [13] Slominski A Zjawiony J Wortsman J Semak I Stewart J Pisarchik A Sweatman T Marcos J Dunbar C Tuckey RC A novel pathway for sequential transformation of 7-dehydrocholesterol and expression of the P450scc system in mammalian skin Eur. J. Biochem./FEBS 2004 271 21 4178 4188 PMC1201497 15511223 source

      Not checked in the free run.

    • cites [21] Slominski A Zbytek B Nikolakis G Manna PR Skobowiat C Zmijewski M Li W Janjetovic Z Postlethwaite A Zouboulis CC Tuckey RC Steroidogenesis in the skin: Implications for local immune functions J. Steroid Biochem. Mol. Biol 2013 137 107 123 23435015 PMC3674137 source

      Not checked in the free run.

    • cites [27] Thiboutot D Jabara S McAllister JM Sivarajah A Gilliland K Cong Z Claw-son G Human skin is a steroidogenic tissue: steroidogenic enzymes and cofactors are expressed in epidermis, normal sebocytes, and an immortalized sebocyte cell line (SEB-1) J. Invest. Dermatol 2003 120 6 905 914 12787114 source

      Not checked in the free run.

    • cites [28] Tiala I Suomela S Huuhtanen J Wakkinen J Holtta-Vuori M Kainu K Ranta S Turpeinen U Hamalainen E Jiao H Karvonen SL Ikonen E Kere J Saarialho-Kere U Elomaa O The CCHCR1 (HCR) gene is relevant for skin steroido-genesis and downregulated in cultured psoriatic keratinocytes J. Mol. Med 2007 85 6 589 601 17221218 source

      Not checked in the free run.

    • cites [29] Inoue T Miki Y Abe K Hatori M Hosaka M Kariya Y Kakuo S Fujimura T Hachiya A Honma S Aiba S Sasano H Sex steroid synthesis in human skin in situ: the roles of aromatase and steroidogenic acute regulatory protein in the homeostasis of human skin Mol. Cell. Endocrinol 2012 362 1–2 19 28 22634420 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    CYP11A1 catalyses the rate-limiting reaction of steroid synthesis, the conversion of cholesterol to pregnenolone.

    “CYP11A1 catalyses the rate-limiting reaction of steroid synthesis, the conversion of cholesterol to pregnenolone”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [17] Tuckey RC Progesterone synthesis by the human placenta Placenta 2005 26 4 273 281 15823613 source

      Not checked in the free run.

    • cites [18] Miller WL Auchus RJ The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders Endocr. Rev 2011 32 1 81 151 21051590 PMC3365799 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    CYP11A1 initiates new vitamin D metabolism pathways in multiple tissues, and the products may have important local or systemic physiological roles.

    “In summary, CYP11A1 initiates new pathways of vitamin D metabolism in a range of tissues and products could have important physiological roles at the local or systemic level.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    CYP11A1 is expressed in the epidermis, adnexal structures, dermis, cultured keratinocytes, melanocytes, sebocytes, dermal fibroblasts, and melanoma cells.

    “CYP11A1 was found to be expressed in the epidermis, adnexal structures and dermis, as well as in cultured keratinocytes, melanocytes, sebocytes, dermal fibroblasts and melanoma cells.”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [13] Slominski A Zjawiony J Wortsman J Semak I Stewart J Pisarchik A Sweatman T Marcos J Dunbar C Tuckey RC A novel pathway for sequential transformation of 7-dehydrocholesterol and expression of the P450scc system in mammalian skin Eur. J. Biochem./FEBS 2004 271 21 4178 4188 PMC1201497 15511223 source

      Not checked in the free run.

    • cites [21] Slominski A Zbytek B Nikolakis G Manna PR Skobowiat C Zmijewski M Li W Janjetovic Z Postlethwaite A Zouboulis CC Tuckey RC Steroidogenesis in the skin: Implications for local immune functions J. Steroid Biochem. Mol. Biol 2013 137 107 123 23435015 PMC3674137 source

      Not checked in the free run.

    • cites [27] Thiboutot D Jabara S McAllister JM Sivarajah A Gilliland K Cong Z Claw-son G Human skin is a steroidogenic tissue: steroidogenic enzymes and cofactors are expressed in epidermis, normal sebocytes, and an immortalized sebocyte cell line (SEB-1) J. Invest. Dermatol 2003 120 6 905 914 12787114 source

      Not checked in the free run.

    • cites [28] Tiala I Suomela S Huuhtanen J Wakkinen J Holtta-Vuori M Kainu K Ranta S Turpeinen U Hamalainen E Jiao H Karvonen SL Ikonen E Kere J Saarialho-Kere U Elomaa O The CCHCR1 (HCR) gene is relevant for skin steroido-genesis and downregulated in cultured psoriatic keratinocytes J. Mol. Med 2007 85 6 589 601 17221218 source

      Not checked in the free run.

    • cites [29] Inoue T Miki Y Abe K Hatori M Hosaka M Kariya Y Kakuo S Fujimura T Hachiya A Honma S Aiba S Sasano H Sex steroid synthesis in human skin in situ: the roles of aromatase and steroidogenic acute regulatory protein in the homeostasis of human skin Mol. Cell. Endocrinol 2012 362 1–2 19 28 22634420 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The major products of vitamin D2 metabolism by CYP11A1 are 20(OH)D2 and 17,20(OH)2D2, with lesser production of 17,20,24(OH)3D2 and an unidentified dihydroxyvitamin D2 metabolite.

    “The major products were identified as 20(OH)D2 and 17,20(OH)2D2, with lesser production of 17,20,24(OH)3D2 and another unidentified dihydroxyvitamin D2 metabolite.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [57] Nguyen MN Slominski A Li W Ng YR Tuckey RC Metabolism of vitamin D2 to 17, 20,24-trihydroxyvitamin D2 by cytochrome p450scc (CYP11A1) Drug Metab. Dispos. Biol. Fate Chem 2009 37 4 761 767 19116262 PMC2659330 source

      Not checked in the free run.

    • cites [58] Slominski A Semak I Wortsman J Zjawiony J Li W Zbytek B Tuckey RC An alternative pathway of vitamin D metabolism. Cytochrome P450scc (CYP11A1)-mediated conversion to 20-hydroxyvitamin D2 and 17,20-dihydroxyvitamin D2 FEBS J 2006 273 13 2891 2901 16817851 PMC1893115 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A metabolite corresponding to 20(OH)D3 is detected in human serum at a level 20 times lower than 25(OH)D3, providing evidence that CYP11A1-mediated vitamin D3 metabolism occurs in vivo.

    “A metabolite corresponding to 20(OH)D3 was also detected in human serum at a level 20 times lower than that of 25(OH)D3, providing further evidence that metabolism of vitamin D3 by CYP11A1 occurs in vivo”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [52] Slominski AT Kim TK Shehabi HZ Semak I Tang EK Nguyen MN Benson HA Korik E Janjetovic Z Chen J Yates CR Postlethwaite A Li W Tuckey RC In vivo evidence for a novel pathway of vitamin D(3) metabolism initiated by P450scc and modified by CYP27B1 FASEB J 2012 26 9 3901 3915 22683847 PMC3425822 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Ex vivo and ex-utero incubations of vitamin D3 with adrenal gland and human placenta fragments demonstrate the same CYP11A1-catalysed reactions, with 20(OH)D3 as the major metabolite.

    “more recent ex vivo and ex-utero incubations of vitamin D3 with fragments of adrenal glands and human placentas (which express CYP11A1) have clearly demonstrated that the same CYP11A-caltalysed reactions occur. These studies show that 20(OH)D3 is produced as the major metabolite”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [52] Slominski AT Kim TK Shehabi HZ Semak I Tang EK Nguyen MN Benson HA Korik E Janjetovic Z Chen J Yates CR Postlethwaite A Li W Tuckey RC In vivo evidence for a novel pathway of vitamin D(3) metabolism initiated by P450scc and modified by CYP27B1 FASEB J 2012 26 9 3901 3915 22683847 PMC3425822 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    CYP27A1 and CYP24A1 can metabolize 20(OH)D3.

    “both CYP27A1 which acts as a 25-hydroxylase on vitamin D3 and a 26-hydroxylase on cholesterol, and CYP24A1 which inactivates 1,25(OH)2D3, can also metabolize 20(OH)D3”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [55] Tieu EW Li W Chen J Baldisseri DM Slominski AT Tuckey RC Metabolism of cholesterol, vitamin D3 and 20-hydroxyvitamin D3 incorporated into phospholipid vesicles by human CYP27A1 J. Steroid Biochem. Mol. Biol 2012 129 3–5 163 171 22210453 PMC3303980 source

      Not checked in the free run.

    • cites [56] Tieu EW Tang EK Chen J Li W Nguyen MN Janjetovic Z Slominski A Tuckey RC Rat CYP24A1 acts on 20-hydroxyvitamin D(3) producing hydroxylated products with increased biological activity Biochem. Pharmacol 2012 84 12 1696 1704 23041230 PMC3501553 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    20,24(OH)2D3, 20,25(OH)2D3, and 20,26(OH)2D3 can be 1α-hydroxylated by CYP27B1 with catalytic efficiency similar to that for 25(OH)D3 and much higher than for the parent 20(OH)D3.

    “20,24(OH)2D3, 20,25(OH)2D3 and 20,26(OH)2D3 can be 1α-hydroxylated by CYP27B1 with a catalytic efficiency similar to that for 1α-hydroxylation of 25(OH)D3 and much higher than for the parent 20(OH)D3”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [53] Tang EK Chen J Janjetovic Z Tieu EW Slominski AT Li W Tuckey RC Hydroxylation of CYP11A1-derived products of vitamin D3 metabolism by human and mouse CYP27B1 Drug Metab. Dispos. Biol. Fate Chem 2013 41 5 1112 1124 23454830 PMC3629803 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Rat CYP24A1 hydroxylates 20(OH)D3 at C24, producing 20,24(OH)2D3 as the major product, and at C25, producing 20,25(OH)2D3.

    “Rat CYP24A1 was observed to hydroxylate 20(OH)D3 at C24, as it does with 1,25(OH)2D3, producing 20,24(OH)2D3 as the major product. It was also found to hydroxylate 20(OH)D3 at C25 producing 20,25(OH)2D3.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [56] Tieu EW Tang EK Chen J Li W Nguyen MN Janjetovic Z Slominski A Tuckey RC Rat CYP24A1 acts on 20-hydroxyvitamin D(3) producing hydroxylated products with increased biological activity Biochem. Pharmacol 2012 84 12 1696 1704 23041230 PMC3501553 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Unlike 1,25(OH)2D3, 20(OH)D3 and 20,23(OH)2D3 only modestly stimulate CYP24A1 transcription and do not markedly induce their own metabolism.

    “However, unlike 1,25(OH)2D3 they only modestly stimulate the transcription of the CYP24A1 gene and thus do not markedly induce their own metabolism by CYP24A1.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [68] Zbytek B Janjetovic Z Tuckey RC Zmijewski MA Sweatman TW Jones E Nguyen MN Slominski AT 20-Hydroxyvitamin D3, a product of vitamin D3 hydroxylation by cytochrome P450scc, stimulates keratinocyte differentiation J. Invest. Dermatol 2008 128 9 2271 2280 18368131 PMC2574837 source

      Not checked in the free run.

    • cites [69] Janjetovic Z Tuckey RC Nguyen MN Thorpe EM Jr. Slominski AT 20, 23-dihydroxyvitamin D3, novel P450scc product, stimulates differentiation and inhibits proliferation and NF-kappaB activity in human keratinocytes J. Cell. Physiol 2010 223 1 36 48 20020487 PMC2814891 source

      Not checked in the free run.

    • cites [70] Janjetovic Z Zmijewski MA Tuckey RC DeLeon DA Nguyen MN Pfeffer LM Slominski AT 20-Hydroxycholecalciferol, product of vitamin D3 hydroxylation by P450scc, decreases NF-kappaB activity by increasing IkappaB alpha levels in human keratinocytes PLoS One 2009 4 6 e5988 19543524 PMC2694402 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    CYP11A1 does not hydroxylate 25(OH)D3, so it does not compete with CYP27B1 for activation of 25-hydroxyvitamin D3.

    “It is important to note that CYP11A1 does not hydroxylate 25(OH)D3 [46] so that the CYP11A1 does not compete with CYP27B1 for activation of 25-hydroxyvitamin D3.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [46] Slominski A Semak I Zjawiony J Wortsman J Li W Szczesniewski A Tuckey RC The cytochrome P450scc system opens an alternate pathway of vitamin D3 metabolism FEBS J 2005 272 16 4080 4090 16098191 PMC2234577 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    CYP11A1 can hydroxylate the prodrug 1(OH)D3 to the biologically active product 1,20(OH)2D3, providing an alternative route to 25-hydroxylation for activation.

    “However, CYP11A1 can hydroxylate the prodrug 1(OH)D3 to the biologically active product, 1,20(OH)2D3, providing an alternative route to 25-hydroxylation for activation of this compound”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [50] Tuckey RC Janjetovic Z Li W Nguyen MN Zmijewski MA Zjawiony J Slominski A Metabolism of 1alpha-hydroxyvitamin D3 by cytochrome P450scc to biologically active 1alpha, 20-dihydroxyvitamin D3 J. Steroid Biochem. Mol. Biol 2008 112 213 219 19000766 PMC2605774 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Purified CYP11A1 hydroxylates the vitamin D2 side chain without cleavage, with the preferred initial site at C20.

    “purified CYP11A1 can also hydroxylate the side chain of vitamin D2 without its cleavage, with the preferred site for the initial hydroxylation being at C20”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [57] Nguyen MN Slominski A Li W Ng YR Tuckey RC Metabolism of vitamin D2 to 17, 20,24-trihydroxyvitamin D2 by cytochrome p450scc (CYP11A1) Drug Metab. Dispos. Biol. Fate Chem 2009 37 4 761 767 19116262 PMC2659330 source

      Not checked in the free run.

    • cites [58] Slominski A Semak I Wortsman J Zjawiony J Li W Zbytek B Tuckey RC An alternative pathway of vitamin D metabolism. Cytochrome P450scc (CYP11A1)-mediated conversion to 20-hydroxyvitamin D2 and 17,20-dihydroxyvitamin D2 FEBS J 2006 273 13 2891 2901 16817851 PMC1893115 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Adrenal and placenta express CYP27A1, CYP2R1, and CYP27B1, and convert vitamin D3 to 25(OH)D3 and 25(OH)D3 to 1,25(OH)2D3.

    “Both the adrenal and placenta express CYP27A1, CYP2R1 and CYP27B1, and convert vitamin D3 to 25(OH)D3, and 25(OH)D3 to 1,25(OH)2D3”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [52] Slominski AT Kim TK Shehabi HZ Semak I Tang EK Nguyen MN Benson HA Korik E Janjetovic Z Chen J Yates CR Postlethwaite A Li W Tuckey RC In vivo evidence for a novel pathway of vitamin D(3) metabolism initiated by P450scc and modified by CYP27B1 FASEB J 2012 26 9 3901 3915 22683847 PMC3425822 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    CYP27B1-dependent 1α-hydroxylations occur in vivo, with 1,20(OH)2D3 and 1,20,23(OH)3D3 identified in ex-utero incubations of placentas and adrenals with vitamin D3.

    “these CYP27B1-dependent 1α-hydroxylations do appear to occur in vivo with 1,20(OH)2D3 and 1,20,23(OH)3D3 being identified in ex-utero incubations of placentas and adrenals with vitamin D3”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [52] Slominski AT Kim TK Shehabi HZ Semak I Tang EK Nguyen MN Benson HA Korik E Janjetovic Z Chen J Yates CR Postlethwaite A Li W Tuckey RC In vivo evidence for a novel pathway of vitamin D(3) metabolism initiated by P450scc and modified by CYP27B1 FASEB J 2012 26 9 3901 3915 22683847 PMC3425822 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    20(OH)D3 and 20,23(OH)2D3 inhibit DNA synthesis and colony formation, cause cell cycle arrest, and stimulate keratinocyte differentiation with potency comparable to 1,25(OH)2D3.

    “These secosteroids inhibit DNA synthesis and colony formation, cause cell cycle arrest and stimulate the differentiation program of keratinocytes with a potency comparable to that of 1,25(OH)2D3.”
    Quote in the paperSubstantial claim0 of 7 sources checked
    • cites [49] Li W Chen J Janjetovic Z Kim TK Sweatman T Lu Y Zjawiony J Tuckey RC Miller D Slominski A Chemical synthesis of 20S-hydroxyvitamin D3, which shows antiproliferative activity Steroids 2010 75 12 926 935 20542050 PMC2937189 source

      Not checked in the free run.

    • cites [68] Zbytek B Janjetovic Z Tuckey RC Zmijewski MA Sweatman TW Jones E Nguyen MN Slominski AT 20-Hydroxyvitamin D3, a product of vitamin D3 hydroxylation by cytochrome P450scc, stimulates keratinocyte differentiation J. Invest. Dermatol 2008 128 9 2271 2280 18368131 PMC2574837 source

      Not checked in the free run.

    • cites [69] Janjetovic Z Tuckey RC Nguyen MN Thorpe EM Jr. Slominski AT 20, 23-dihydroxyvitamin D3, novel P450scc product, stimulates differentiation and inhibits proliferation and NF-kappaB activity in human keratinocytes J. Cell. Physiol 2010 223 1 36 48 20020487 PMC2814891 source

      Not checked in the free run.

    • cites [70] Janjetovic Z Zmijewski MA Tuckey RC DeLeon DA Nguyen MN Pfeffer LM Slominski AT 20-Hydroxycholecalciferol, product of vitamin D3 hydroxylation by P450scc, decreases NF-kappaB activity by increasing IkappaB alpha levels in human keratinocytes PLoS One 2009 4 6 e5988 19543524 PMC2694402 source

      Not checked in the free run.

    • cites [71] Slominski A Li W Zbytek B Tuckey RC Zjawiony J Nguyen MN Janjetovic Z Zmijewski M Sweatman T Miller D Chen J Postlethwaite A Enzymatic production or chemical synthesis and uses for 5,7-dienes and UVB conversion products thereof 2011 US2011/0118228A1

      Not checked in the free run.

    • cites [72] Lu Y Chen J Janjetovic Z Michaels P Tang EK Wang J Tuckey RC Slominski AT Li W Miller DD Design, synthesis, and biological action of 20R-hydroxyvitamin D3 J. Med. Chem 2012 55 7 3573 3577 22404326 PMC3332540

      Not checked in the free run.

    • cites [73] Kim TK Wang J Janjetovic Z Chen J Tuckey RC Nguyen MN Tang EK Miller D Li W Slominski AT Correlation between secosteroid-induced vitamin D receptor activity in melanoma cells and computer-modeled receptor binding strength Mol. Cell. Endocrinol 2012 361 1–2 143 152 22546549 PMC3409337 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    7DHP produced locally by CYP11A1 action on 7DHC can serve as a substrate for production of Δ7-pregnenes, -androgens, and -estrogens, which have been identified in patients with Smith-Lemli-Opitz Syndrome.

    “7DHP produced locally by the action of CYP11A1 on 7DHC, can further serve as the substrate for the production of Δ7-pregnenes, -androgens and -estrogens, which have been identified in patients with Smith–Lemli–Opitz Syndrome (SLOS)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [61] Shackleton C Roitman E Guo LW Wilson WK Porter FD Identification of 7(8) and 8(9) unsaturated adrenal steroid metabolites produced by patients with 7-dehydrosterol-delta7-reductase deficiency (Smith–Lemli–Opitz syndrome) J. Steroid Biochem. Mol. Biol 2002 82 2–3 225 232 12477489

      Not checked in the free run.

    • cites [62] Marcos J Guo LW Wilson WK Porter FD Shackleton C The implications of 7-dehydrosterol-7-reductase deficiency (Smith–Lemli–Opitz syndrome) to neurosteroid production Steroids 2004 69 1 51 60 14715377

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In normal melanocytes, addition of a 1α-hydroxyl group to 20(OH)D3 potentiates inhibition of proliferation and inhibits dendrite formation.

    “In normal melanocytes addition of a 1α-hydroxyl group to 20(OH)D3 potentiated the inhibitory effect on proliferation and inhibited dendrite formation.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [78] Slominski AT Janjetovic Z Kim TK Wright AC Grese LN Riney SJ Nguyen MN Tuckey RC Novel vitamin D hydroxyderivatives inhibit melanoma growth and show differential effects on normal melanocytes Anticancer Res 2012 32 9 3733 3742 22993313 PMC3458587

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Addition of a 1α-hydroxyl group to 20,25(OH)2D3 by CYP27B1 further increases anti-melanoma activity, with the opposite effect for 1α-hydroxylation of 20,26(OH)2D3.

    “Addition of a 1α-hydroxyl group to 20,25(OH)2D3 by CYP27B1 further increased this anti-melanoma activity with the opposite effect seen for 1α-hydroxylation of 20,26(OH)2D3”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [53] Tang EK Chen J Janjetovic Z Tieu EW Slominski AT Li W Tuckey RC Hydroxylation of CYP11A1-derived products of vitamin D3 metabolism by human and mouse CYP27B1 Drug Metab. Dispos. Biol. Fate Chem 2013 41 5 1112 1124 23454830 PMC3629803 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Stimulation of melanogenesis increases the antiproliferative effect of some short side chain secosteroids, in contrast to 20(OH)D3 where the effect is opposite.

    “The stimulation of melanogenesis appeared to increase the antiproliferative effect of some of the secosteroids with a short side chain [64,65], which is in contrast to 20(OH)D3 where the effect was opposite”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [64] Zmijewski MA Li W Zjawiony JK Sweatman TW Chen J Miller DD Slominski AT Photo-conversion of two epimers (20R and 20S) of pregna-5, 7-diene-3 beta, 17 alpha, 20-triol and their bioactivity in melanoma cells Steroids 2009 74 2 218 228 19028513 PMC2631623 source

      Not checked in the free run.

    • cites [65] Zmijewski MA Li W Chen J Kim T-K Zjawiony JK Sweatman TW Miller DD Slominski AT Synthesis and photochemical transformation of 3 beta, 21-dihydroxypregna-5,7-dien-20-one to novel secosteroids that show anti-melanoma activity Steroids 2011 76 1-2 193 203 21070794 PMC3005096 source

      Not checked in the free run.

    • cites [77] Janjetovic Z Brozyna AA Tuckey RC Kim TK Nguyen MN Jozwicki W Pfeffer SR Pfeffer LM Slominski AT High basal NF-kappaB activity in nonpigmented melanoma cells is associated with an enhanced sensitivity to vitamin D3 derivatives Br. J. Cancer 2011 105 12 1874 1884 22095230 PMC3251881 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    VDR and CYP27B1 expression decrease during melanoma progression, and melanization and melanogenesis negatively affect overall and stage III disease survival.

    “expression of the VDR and CYP27B1 decreased during melanoma progression, and melanization and melanogenesis negatively affected both overall- and stage III disease-survival”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [79] Brozyna AA Jozwicki W Carlson JA Slominski AT Melanogenesis affects overall and disease-free survival in patients with stage III and IV melanoma Human Pathol 2013 44 10 2071 2074 23791398 PMC3783651 source

      Not checked in the free run.

    • cites [80] Brozyna AA Jozwicki W Janjetovic Z Slominski AT Expression of the vita-min D-activating enzyme 1alpha-hydroxylase (CYP27B1) decreases during melanoma progression Human Pathol 2013 44 3 374 387 22995334 PMC3529817 source

      Not checked in the free run.

    • cites [81] Brozyna AA Jozwicki W Janjetovic Z Slominski AT Expression of vitamin D receptor decreases during progression of pigmented skin lesions Human Pathol 2011 42 5 618 631 21292298 PMC3078192 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Secosteroids with a short side chain and their 5,7-diene precursors inhibit keratinocyte proliferation and NF-κB activation, with 5,7-dienes more potent than their secosteroidal derivatives.

    “while they inhibited proliferation of keratinocytes and activation of NF-κB, activity 5,7-dienes were more potent than their 9,10-secosteroidal derivatives”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [41] Slominski AT Zmijewski MA Semak I Sweatman T Janjetovic Z Li W Zjawiony JK Tuckey RC Sequential metabolism of 7-dehydrocholesterol to steroidal 5, 7-dienes in adrenal glands and its biological implication in the skin PLoS One 2009 4 2 e4309 19190754 PMC2629546 source

      Not checked in the free run.

    • cites [63] Slominski A Kim TK Zmijewski MA Janjetovic Z Li W Chen J Kusniatsova EI Semak I Postlethwaite A Miller D Zjawiony J Tuckey RC Novel vitamin D photoproducts and their precursors in the skin Dermatoendocrinology 2013 5 1 7 19 PMC3897599 24494038 source

      Not checked in the free run.

    • cites [71] Slominski A Li W Zbytek B Tuckey RC Zjawiony J Nguyen MN Janjetovic Z Zmijewski M Sweatman T Miller D Chen J Postlethwaite A Enzymatic production or chemical synthesis and uses for 5,7-dienes and UVB conversion products thereof 2011 US2011/0118228A1

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    20(OH)D3 and 20,23(OH)2D3 inhibit NF-κB activity in normal and immortalized keratinocytes and have anti-inflammatory properties.

    “20(OH)D3 and 20,23(OH)2D3 inhibit NF-κB activity in normal and immortalized keratinocytes and have anti-inflammatory properties”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [69] Janjetovic Z Tuckey RC Nguyen MN Thorpe EM Jr. Slominski AT 20, 23-dihydroxyvitamin D3, novel P450scc product, stimulates differentiation and inhibits proliferation and NF-kappaB activity in human keratinocytes J. Cell. Physiol 2010 223 1 36 48 20020487 PMC2814891 source

      Not checked in the free run.

    • cites [70] Janjetovic Z Zmijewski MA Tuckey RC DeLeon DA Nguyen MN Pfeffer LM Slominski AT 20-Hydroxycholecalciferol, product of vitamin D3 hydroxylation by P450scc, decreases NF-kappaB activity by increasing IkappaB alpha levels in human keratinocytes PLoS One 2009 4 6 e5988 19543524 PMC2694402 source

      Not checked in the free run.

    • cites [71] Slominski A Li W Zbytek B Tuckey RC Zjawiony J Nguyen MN Janjetovic Z Zmijewski M Sweatman T Miller D Chen J Postlethwaite A Enzymatic production or chemical synthesis and uses for 5,7-dienes and UVB conversion products thereof 2011 US2011/0118228A1

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Secosteroids with a short side chain have lower potency for inhibiting melanocyte proliferation than those with a full 8-carbon side chain, but similar inhibitory potency on melanoma cells.

    “secosteroids with a short side chain showed lower potency for the inhibition of melanocyte proliferation than those with a full (8 carbon) side chain, but had similar inhibitory potency on melanoma cells”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [63] Slominski A Kim TK Zmijewski MA Janjetovic Z Li W Chen J Kusniatsova EI Semak I Postlethwaite A Miller D Zjawiony J Tuckey RC Novel vitamin D photoproducts and their precursors in the skin Dermatoendocrinology 2013 5 1 7 19 PMC3897599 24494038 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    In the case of CYP24A1, the increased potency of its 20(OH)D3 products indicates that the enzyme plays an activating role, rather than the inactivation seen with 1,25(OH)2D3.

    “In the case of CYP24A1, the increased potency of the products indicates that the enzyme plays an activating role, rather than the inactivation seen with 1,25(OH)2D3.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [56] Tieu EW Tang EK Chen J Li W Nguyen MN Janjetovic Z Slominski A Tuckey RC Rat CYP24A1 acts on 20-hydroxyvitamin D(3) producing hydroxylated products with increased biological activity Biochem. Pharmacol 2012 84 12 1696 1704 23041230 PMC3501553 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In human SKMEL-188 melanoma cells, inhibition of growth by 20(OH)D3 is accompanied by inhibition of NF-κB activity, with a more pronounced effect on amelanotic than fully melanized cells.

    “In human SKMEL-188 melanoma cells, inhibition of growth by 20(OH)D3 was accompanied by inhibition of NF-κB activity with a more pronounced effect on amelanotic than fully melanized cells”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [77] Janjetovic Z Brozyna AA Tuckey RC Kim TK Nguyen MN Jozwicki W Pfeffer SR Pfeffer LM Slominski AT High basal NF-kappaB activity in nonpigmented melanoma cells is associated with an enhanced sensitivity to vitamin D3 derivatives Br. J. Cancer 2011 105 12 1874 1884 22095230 PMC3251881 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Stimulation of IκBα expression sequesters NF-κB in the cytoplasm and attenuates its transcriptional activity.

    “Thus, stimulation of the expression of IκBα sequesters NF-κB in the cytoplasm and attenuates its transcriptional activity.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [69] Janjetovic Z Tuckey RC Nguyen MN Thorpe EM Jr. Slominski AT 20, 23-dihydroxyvitamin D3, novel P450scc product, stimulates differentiation and inhibits proliferation and NF-kappaB activity in human keratinocytes J. Cell. Physiol 2010 223 1 36 48 20020487 PMC2814891 source

      Not checked in the free run.

    • cites [70] Janjetovic Z Zmijewski MA Tuckey RC DeLeon DA Nguyen MN Pfeffer LM Slominski AT 20-Hydroxycholecalciferol, product of vitamin D3 hydroxylation by P450scc, decreases NF-kappaB activity by increasing IkappaB alpha levels in human keratinocytes PLoS One 2009 4 6 e5988 19543524 PMC2694402 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    1α-hydroxylated products 1,20(OH)2D3, 1,20(OH)2D2, and 1,20,23(OH)3D3 show similar inhibition of keratinocyte proliferation and stimulation of differentiation and VDR expression to their precursors, but greater stimulation of CYP24A1 expression.

    “These products show similar inhibition of keratinocyte proliferation and stimulation of differentiation and VDR expression to those of their precursors, but display greater stimulation of CYP24A1 expression”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [50] Tuckey RC Janjetovic Z Li W Nguyen MN Zmijewski MA Zjawiony J Slominski A Metabolism of 1alpha-hydroxyvitamin D3 by cytochrome P450scc to biologically active 1alpha, 20-dihydroxyvitamin D3 J. Steroid Biochem. Mol. Biol 2008 112 213 219 19000766 PMC2605774 source

      Not checked in the free run.

    • cites [59] Slominski AT Kim TK Janjetovic Z Tuckey RC Bieniek R Yue J Li W Chen J Nguyen MN Tang EK Miller D Chen TC Holick M 20-Hydroxyvitamin D2 is a noncalcemic analog of vitamin D with potent antiproliferative and prodifferentiation activities in normal and malignant cells Am. J. Physiol. Cell Physiol 2011 300 3 C526 C541 21160030 PMC3063966 source

      Not checked in the free run.

    • cites [71] Slominski A Li W Zbytek B Tuckey RC Zjawiony J Nguyen MN Janjetovic Z Zmijewski M Sweatman T Miller D Chen J Postlethwaite A Enzymatic production or chemical synthesis and uses for 5,7-dienes and UVB conversion products thereof 2011 US2011/0118228A1

      Not checked in the free run.

    • cites [73] Kim TK Wang J Janjetovic Z Chen J Tuckey RC Nguyen MN Tang EK Miller D Li W Slominski AT Correlation between secosteroid-induced vitamin D receptor activity in melanoma cells and computer-modeled receptor binding strength Mol. Cell. Endocrinol 2012 361 1–2 143 152 22546549 PMC3409337 source

      Not checked in the free run.

    • cites [74] Tang EK Li W Janjetovic Z Nguyen MN Wang Z Slominski A Tuckey RC Purified mouse CYP27B1 can hydroxylate 20,23-dihydroxyvitamin D3, producing 1alpha,20,23-trihydroxyvitamin D3, which has altered biological activity Drug Metab. Dispos. Biol. Fate Chem 2010 38 9 1553 1559 20554701 PMC2939470 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    22(OH)2D3 and 20,22(OH)2D3 show antiproliferative and prodifferentiation effects but are less potent than 20(OH)D3 and 20,23(OH)2D3.

    “The CYP11A1-derived secosteroids with a 22-hydroxyl group, 22(OH)2D3 and 20,22(OH)2D3, also show both antiproliferative and prodifferentiation effects, but are less potent than 20(OH)D3 and 20,23(OH)2D3”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [48] Tuckey RC Li W Shehabi HZ Janjetovic Z Nguyen MN Kim TK Chen J Howell DE Benson HA Sweatman T Baldisseri DM Slominski A Production of 22-hydroxy metabolites of vitamin D3 by cytochrome p450scc (CYP11A1) and analysis of their biological activities on skin cells Drug Metab. Dispos. Biol. Fate Chem 2011 39 9 1577 1588 21677063 PMC3164270 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    7DHP inhibits HaCaT keratinocyte proliferation in a dose-dependent manner, while pregnacalciferol shows little or no antiproliferative activity.

    “7DHP inhibited the proliferation of HaCaT keratinocytes in a dose-dependent manner, with pregnacalciferol (pD) showing little or no antiproliferative activity”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [40] Slominski AT Kim TK Chen J Nguyen MN Li W Yates CR Sweatman T Janjetovic Z Tuckey RC Cytochrome P450scc-dependent metabolism of 7-dehydrocholesterol in placenta and epidermal keratinocytes Int. J. Biochem. Cell Biol 2012 44 11 2003 2018 22877869 PMC3520099 source

      Not checked in the free run.

    • cites [41] Slominski AT Zmijewski MA Semak I Sweatman T Janjetovic Z Li W Zjawiony JK Tuckey RC Sequential metabolism of 7-dehydrocholesterol to steroidal 5, 7-dienes in adrenal glands and its biological implication in the skin PLoS One 2009 4 2 e4309 19190754 PMC2629546 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The compounds show potent antimelanoma activity, as evaluated by inhibition of proliferation, colony formation, and soft agar growth, similar to or higher than 1,25(OH)2D3.

    “The above compounds also showed potent antimelanoma activity, as evaluated by inhibition of proliferation, colony formation in monolayer (plating efficiency) and soft agar assays (anchorage independent growth), that was similar to or higher than that seen for 1,25(OH)2D3”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [59] Slominski AT Kim TK Janjetovic Z Tuckey RC Bieniek R Yue J Li W Chen J Nguyen MN Tang EK Miller D Chen TC Holick M 20-Hydroxyvitamin D2 is a noncalcemic analog of vitamin D with potent antiproliferative and prodifferentiation activities in normal and malignant cells Am. J. Physiol. Cell Physiol 2011 300 3 C526 C541 21160030 PMC3063966 source

      Not checked in the free run.

    • cites [63] Slominski A Kim TK Zmijewski MA Janjetovic Z Li W Chen J Kusniatsova EI Semak I Postlethwaite A Miller D Zjawiony J Tuckey RC Novel vitamin D photoproducts and their precursors in the skin Dermatoendocrinology 2013 5 1 7 19 PMC3897599 24494038 source

      Not checked in the free run.

    • cites [71] Slominski A Li W Zbytek B Tuckey RC Zjawiony J Nguyen MN Janjetovic Z Zmijewski M Sweatman T Miller D Chen J Postlethwaite A Enzymatic production or chemical synthesis and uses for 5,7-dienes and UVB conversion products thereof 2011 US2011/0118228A1

      Not checked in the free run.

    • cites [77] Janjetovic Z Brozyna AA Tuckey RC Kim TK Nguyen MN Jozwicki W Pfeffer SR Pfeffer LM Slominski AT High basal NF-kappaB activity in nonpigmented melanoma cells is associated with an enhanced sensitivity to vitamin D3 derivatives Br. J. Cancer 2011 105 12 1874 1884 22095230 PMC3251881 source

      Not checked in the free run.

    • cites [78] Slominski AT Janjetovic Z Kim TK Wright AC Grese LN Riney SJ Nguyen MN Tuckey RC Novel vitamin D hydroxyderivatives inhibit melanoma growth and show differential effects on normal melanocytes Anticancer Res 2012 32 9 3733 3742 22993313 PMC3458587

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    20(OH)D2 inhibits proliferation and induces the differentiation program of keratinocytes.

    “Studies on vitamin D2-derived 20(OH)D2 have demonstrated that it can also inhibit proliferation and induce the differentiation program of keratinocytes”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [59] Slominski AT Kim TK Janjetovic Z Tuckey RC Bieniek R Yue J Li W Chen J Nguyen MN Tang EK Miller D Chen TC Holick M 20-Hydroxyvitamin D2 is a noncalcemic analog of vitamin D with potent antiproliferative and prodifferentiation activities in normal and malignant cells Am. J. Physiol. Cell Physiol 2011 300 3 C526 C541 21160030 PMC3063966 source

      Not checked in the free run.

    • cites [71] Slominski A Li W Zbytek B Tuckey RC Zjawiony J Nguyen MN Janjetovic Z Zmijewski M Sweatman T Miller D Chen J Postlethwaite A Enzymatic production or chemical synthesis and uses for 5,7-dienes and UVB conversion products thereof 2011 US2011/0118228A1

      Not checked in the free run.

    • cites [73] Kim TK Wang J Janjetovic Z Chen J Tuckey RC Nguyen MN Tang EK Miller D Li W Slominski AT Correlation between secosteroid-induced vitamin D receptor activity in melanoma cells and computer-modeled receptor binding strength Mol. Cell. Endocrinol 2012 361 1–2 143 152 22546549 PMC3409337 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    20R(OH)D3 behaves similarly to 20S(OH)D3 at high concentrations but stimulates rather than inhibits proliferation at low (0.1 nM) concentrations.

    “whereas the 20R(OH)D3 epimer behaves similarly to 20S(OH)D3 at high concentrations, but stimulates rather than inhibits proliferation at low (0.1 nM) concentrations”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [72] Lu Y Chen J Janjetovic Z Michaels P Tang EK Wang J Tuckey RC Slominski AT Li W Miller DD Design, synthesis, and biological action of 20R-hydroxyvitamin D3 J. Med. Chem 2012 55 7 3573 3577 22404326 PMC3332540

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    They also show anti-leukemic activities, with full-length side chain secosteroids displaying significantly stronger prodifferentiation and antiproliferative effects than pD and pL derivatives.

    “They also showed anti-leukemic activities, with secosteroids having a full-length side chain displaying significantly stronger prodifferentiation and antiproliferative effects than the pD and pL derivatives”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [84] Slominski AT Janjetovic Z Fuller BE Zmijewski MA Tuckey RC Nguyen MN Sweatman T Li W Zjawiony J Miller D Chen TC Lozanski G Holick MF Products of vitamin D3 or 7-dehydrocholesterol metabolism by cytochrome P450scc show anti-leukemia effects, having low or absent calcemic activity PLoS One 2010 5 3 e9907 20360850 PMC2845617 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Some CYP11A1-derived secosteroids may act as endogenous VDR ligands, potentially explaining why VDR-/- mice develop alopecia while CYP27B1-/- mice do not.

    “Some of the CYP11A1-derived secosteroids may serve as endogenous ligands for the VDR providing a potential explanation for why VDR–/– mice develop alopecia while CYP27B1–/– do not, i.e., an endogenous ligand other than 1,25(OH)2D3 that does not require 1α-hydroxylation may activate the VDR locally.”
    Quote in the paperSubstantial claim
61 of 61

  • The paper relies on this without support.

    The collagen-induced arthritis model in DBA/1 Lac J mice is a valid model of human rheumatoid arthritis.

    “the DBA/1 Lac J CIA model of rheumatoid arthritis (RA)”

  • The paper relies on this without support.

    Effects of CYP11A1-derived secosteroids observed in cell culture and mouse models are predictive of therapeutic effects in humans.

    “could serve both as endogenous regulators of skin functions and as excellent candidates for treatment of hyperproliferative and inflammatory skin disorders, and skin cancer”

  • The paper relies on this without support.

    The absence of calcemic toxicity in rodents at pharmacological doses indicates that these secosteroids will be safe in humans.

    “20(OH)D3 and 20,23(OH)2D3 are non-calcemic at pharmacological doses”

  • The paper relies on this without support.

    Findings on calcemic and toxic effects in rodents predict the safety profile of these secosteroids in humans.

    “The metabolites display high biological potencies with specific effects dependent on cell lineage, and show a lack of calcemic or other toxic effects at pharmacological doses far above the toxicity levels of 25(OH)D3 or 1,25(OH)2D3.”

  • The paper relies on this without support.

    Effects observed in cell and animal models translate to human skin disorders.

    “In the skin, these novel secosteroids could serve both as endogenous regulators of skin functions and as excellent candidates for treatment of hyper-proliferative, fibrosing and inflammatory skin disorders including psoriasis and skin cancer.”
5 of 5

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Previous studies demonstrated anti-proliferative effects of hydroxy-derivatives of vitamin D3 and hydroxylumisterols on keratinocytes.

    “Our previous studies demonstrated the anti-proliferative effects of hydroxy-derivatives of vitamin D3 [40,41,77] and hydroxylumisterols on keratinocytes [45].”

    From Protective Effects of Novel Derivatives of Vitamin D3 and Lumisterol Against UVB-Induced Damage in Human Keratinocytes Involve Activation of Nrf2 and P53 Defense Mechanisms (2019) · cites this paper as [41]

  • CYP11A1 favors initial hydroxylation of vitamin D3 at C20 over C22 (or C23), with 20(OH)D3 as the first and major metabolite.

    “Subsequent enzymatic analysis revealed that CYP11A1 favors initial hydroxylation of D3 at C20 over C22 (or C23), with 20(OH)D3 representing the first and major metabolite.”

    From Novel activities of CYP11A1 and their potential physiological significance (2015) · cites this paper as [103]

  • CYP11A1-dependent metabolism of vitamin D3 occurs in cells with relatively low expression of this enzyme, such as human and pig epidermal keratinocytes and colonic Caco-2 cells.

    “We also detected CYP11A1-dependent metabolism of D3 in cells with a relatively low expression of this enzyme such as human and pig epidermal keratinocytes [27], and colonic Caco-2 cells [103].”

    From Novel activities of CYP11A1 and their potential physiological significance (2015) · cites this paper as [103]

  • The products of CYP11A1 action on vitamin D can be further hydroxylated by CYP27B1, CYP27A1, and CYP24A1, providing an alternative to the classical pathway, although its physiological importance remains to be established.

    “The products can be further hydroxylated by CYP27B1, CYP27A1, and CYP24A1 (reviewed in [103], and see below), which is an alternative to the classical pathway (see above), although its physiological importance remains to be established.”

    From Novel activities of CYP11A1 and their potential physiological significance (2015) · cites this paper as [103]

  • CYP11A1 does not metabolize 25-hydroxyvitamin D3, indicating that hydroxylation at C25 protects the secosteroid against side chain hydroxylation by CYP11A1, and therefore this enzyme does not compete with CYP27B1 for activation of 25(OH)D3.

    “Importantly, CYP11A1 does not metabolize 25-hydroxyvitamin D3 indicating that hydroxylation at C25 protects the secosteroid against hydroxylation of the side chain by CYP11A1 [24] and therefore, that this enzyme does not compete with CYP27B1 for activation of 25(OH)D3 [103].”

    From Novel activities of CYP11A1 and their potential physiological significance (2015) · cites this paper as [103]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Vitamin D2 metabolite listed in a vitamin D3-only incubation

    Minor

    The keratinocyte experiment is described as incubation with vitamin D3 yielding vitamin D3 hydroxy-derivatives, but the subsequent comparison names 22(OH)D2. The corresponding metabolite listed elsewhere for these incubations is 22(OH)D3.

  • Docking score conflicts with claimed improvement in binding

    Minor

    The paper says more negative docking scores predict better binding. It nevertheless calls a score of positive 14.75 an improvement over the parent compound's score of −12.86.

2 of 2

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Slominski, 2000, Neuroendocrinology of the skin, Endocr. Rev., 21, 457

Cited by

Sorted by citations

Related

Authors
Slominski, A. T., Kim, T.-K., Li, W., Yi, A.-K., Postlethwaite, A., & Tuckey, R. C.
Affiliations
  • University of Tennessee Health Science Center (US)
  • United States Department of Veterans Affairs (US)
  • The University of Western Australia (AU)
Corresponding author
Slominski, Andrzej T.
ORCID
Venue
The Journal of Steroid Biochemistry and Molecular Biology
Publisher
Elsevier BV
Published
2014-10
Volume
144
Pages
28-39
ISSN
0960-0760 (ISSN-L)
DOI
10.1016/j.jsbmb.2013.10.012
PMC
PMC4002668
OpenAlex
W1976466424
Semantic Scholar
dd7538d846f1f724e28fcc3dd5f6e814adffa010
Cited by
170
References
96
Citations by year
2026: 5 · 2025: 11 · 2024: 9 · 2023: 12 · 2022: 18 · 2021: 15 · 2020: 15 · 2019: 6 · 2018: 7 · 2017: 12 · 2016: 20 · 2015: 22 · 2014: 18
FWCI
2.99
Type
journal article
Language
en
Open access
Licence
Locations
  • The Journal of Steroid Biochemistry and Molecular Biology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • UWA Profiles and Research Repository (UWA) (submittedVersion)
Funders
  • National Science Foundation
  • U.S. Department of Veterans Affairs (IP1 BX001607)
  • National Institutes of Health
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R21AR066505, R01AR052190, R21AR063242, R01AR056666)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Vitamin D Research Studies
  • Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Steroid Chemistry and Biochemistry
Keywords
CYP11A1, secosteroids, epidermal keratinocytes, keratinocyte differentiation, cell proliferation, NF-κB inhibition, vitamin D receptor, Caco-2 cells, CYP27B1
MeSH terms
Animals, Cholesterol Side-Chain Cleavage Enzyme, Epidermis, Humans, Secosteroids, Vitamin D, Vitamins

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-06.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-06.

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