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Cited by 57Skin Protection and AgingAntioxidant Activity and Oxidative StressEffects of Radiation Exposure

The Effect of Lycopene Preexposure on UV‐B‐Irradiated Human Keratinocytes

Open access
Ascenso, Andreia, Pedrosa, Tiago, Pinho, Sónia, Pinho, Francisco, Oliveira, José Miguel P. Ferreira de, Cabral Marques, Helena, Oliveira, Helena, Simões, Sandra +1 more·2016·Oxidative Medicine and Cellular Longevity
DOI 10.1155/2016/8214631PMC PMC4664803
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Abstract

Lycopene has been reported as the antioxidant most quickly depleted in skin upon UV irradiation, and thus it might play a protective role. Our goal was to investigate the effects of preexposure to lycopene on UV‐B‐irradiated skin cells. Cells were exposed for 24 h to 10 M lycopene, and subsequently irradiated and left to recover for another 24 h period. Thereafter, several parameters were analyzed by FCM and RT‐PCR: genotoxicity/clastogenicity by assessing the cell cycle distribution; apoptosis by performing the Annexin‐V assay and analyzing gene expression of apoptosis biomarkers; and oxidative stress by ROS quantification. Lycopene did not significantly affect the profile of apoptotic, necrotic and viable cells in nonirradiated cells neither showed cytostatic effects. However, irradiated cells previously treated with lycopene showed an increase in both dead and viable subpopulations compared to nonexposed irradiated cells. In irradiated cells, lycopene preexposure resulted in overexpression of BAX gene compared to nonexposed irradiated cells. This was accompanied by a cell cycle delay at S‐phase transition and consequent decrease of cells in G0/G1 phase. Thus, lycopene seems to play a corrective role in irradiated cells depending on the level of photodamage. Thus, our findings may have implications for the management of skin cancer.

AI snapshot

Written from the paper’s full text.

TL;DR

In HaCaT keratinocytes, 10 μM lycopene complexed with dimethyl-β-cyclodextrin did not affect viability or cell-cycle/apoptosis profiles in nonirradiated cells, but after UV-B irradiation (225 mJ/cm²) it shifted cells toward death and increased BAX expression. The authors conclude lycopene may have a corrective/cytotoxic role in photodamaged keratinocytes, though cyclodextrin vehicle interference limits interpretation.

Key findings

  • Complexed lycopene up to 15 μM did not affect metabolic activity of nonirradiated HaCaT cells, while 20 μM significantly decreased it; 10 μM was selected for further experiments.
  • In nonirradiated cells, lycopene did not significantly affect apoptotic, necrotic, or viable subpopulations and showed no cytostatic effect.
  • In UV-B-irradiated cells (225 mJ/cm²), lycopene preexposure decreased Annexin V-positive early/late apoptotic cells and increased necrotic cells (P < 0.05), with an increase in both dead and viable subpopulations versus nonexposed irradiated cells.
  • Irradiated cells preexposed to lycopene showed increased proapoptotic BAX expression, lower CASP3 expression than nonexposed irradiated cells but higher than CD vehicle, no BCL2 inhibition, and reversion of CD-mediated TRAIL inhibition; cell cycle showed decreased G0/G1 and increased sub-G0/G1, with a trend for S-phase delay.
  • Lycopene did not increase ROS in nonirradiated cells but significantly increased ROS in irradiated cells compared with irradiated nonexposed cells.

Methods

  • Nontumorigenic human keratinocyte HaCaT cells were preexposed for 24 h to 10 μM lycopene complexed with dimethyl-β-cyclodextrin (DM-β-CD), then irradiated with UV-B at 225 mJ/cm² and allowed to recover for 24 h.
  • Dose selection used MTT assays across UV-B doses (~75–325 mJ/cm²) and lycopene concentrations (0–20 μM); endpoints included MTT metabolic activity, flow-cytometry cell cycle analysis with propidium iodide, Annexin V-FITC/PI apoptosis assay, ROS quantification with H2DCF-DA, and RT-qPCR for BAX, BCL2, CASP3, and TNFSF10 (TRAIL) relative to SDHA.
  • Statistical analysis used ANOVA with multiple comparison procedures; significance set at P < 0.05, with at least three replicates/treatment and at least three independent assays for most analyses.

Limitations

  • The paper states that only adherent cells were analyzed, so necrotic cells in suspension were not considered; the high UV-B dose was chosen to induce alterations without excessive necrosis.
  • The paper states that cyclodextrin alone interfered with some in vitro assays and with cells after high UV damage, and that lycopene delivery/stability remains challenging; it calls for normal cells, 3D skin models, other biomarkers, and lower UV-B doses in future work.
  • Evident from the text: findings are from a single aneuploid, nontumorigenic HaCaT cell line, with one lycopene dose and one UV-B dose/time point, and without protein-level or in vivo validation.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1155/2016/8214631

Cites

Statistics

Nothing to recompute.

Claims the paper makes

0 of 46 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    UV-B light decreased TRAIL expression in this study.

    “TRAIL is a proapoptotic cytokine secreted by many cell types; however, in this study, UVB light was found to decrease TRAIL expression.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Complexed lycopene up to 15 μM did not affect the metabolic activity of nonirradiated HaCaT cells.

    “Complexed lycopene (Lyc-CD) up to 15 μM did not affect the metabolic activity of nonirradiated cells”
    Quote in the paperSubstantial claim
  • Findingown data

    UV-B irradiation alone increased the percentage of both early and late apoptotic HaCaT cells compared to control.

    “Contrarily, UV-B irradiation alone increased the percentage of both early and late apoptotic cells (P < 0.05) and decreased the percentage of viable cells compared to the control.”
    Quote in the paperSubstantial claim
  • Findingown data

    Complexed lycopene did not increase ROS production in nonirradiated HaCaT cells.

    “Complexed lycopene did not increase ROS production in nonirradiated cells.”
    Quote in the paperNot a substantial claim
  • Findingown data

    In UV-B irradiated HaCaT cells, Lyc-CD increased CASP3 gene expression compared to CD vehicle.

    “Moreover, in irradiated cells Lyc-CD showed lower caspase 3 gene (CASP3) gene expression compared to nonexposed, irradiated cells; however, it increased CASP3 gene expression comparatively to CD vehicle.”
    Quote in the paperSubstantial claim
  • May combine two claims. 20
  • Classified as probably not a substantial claim. 25

  • May combine two claims.

    Findingown data

    HaCaT cell exponential phase extends until approximately 72 h and full confluence can be maintained more than 1 week.

    “As it can be observed, the exponential phase extends until approximately 72 h and the full confluence can be maintained more than 1 week.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In UV-B irradiated HaCaT cells, preexposure to lycopene increased both dead and viable subpopulations compared to nonexposed irradiated cells.

    “However, irradiated cells previously treated with lycopene showed an increase in both dead and viable subpopulations compared to nonexposed irradiated cells.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    At 10 μM complexed lycopene, HaCaT cell metabolic activity was higher than 50% and was not significantly different from nonexposed cells.

    “At this lycopene concentration, the cell metabolic activity was higher than 50% and was not significantly different from the nonexposed cells.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Irradiated cells showed significantly higher levels of apoptosis, confirmed by increased sub-G1 population and Annexin V binding.

    “In this work, irradiated cells showed significantly higher levels of apoptosis, confirmed by independent parameters (namely, increased sub-G1 population indicative of DNA fragmentation) and binding to Annexin V, indicative of increased phosphatidylserine present in the outer leaflet of the cell membrane.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    BCL2 was found upregulated and TRAIL was found downregulated under UVB irradiation.

    “BCL2, a known antiapoptotic effector was found upregulated in this study, and TRAIL, a proapoptotic cytokine, was found downregulated under UVB irradiation.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    At nontoxic dose (10 μM), complexed lycopene does not affect the profile of apoptotic, necrotic, and viable cells or show cytostatic effects despite slightly increasing the ROS content.

    “On one hand, at nontoxic dose (10 μM) complexed lycopene does not affect the profile of apoptotic, necrotic, and viable cells or show cytostatic effects despite slightly increasing the ROS content.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Lycopene has been shown to inhibit proliferation of several types of cancer cells through different mechanisms in in vitro systems.

    “In fact, lycopene has been shown to inhibit proliferation of several types of cancer cells through different mechanisms in in vitro systems [10, 11].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [10] Salman H. Bergman M. Djaldetti M. Bessler H. Lycopene affects proliferation and apoptosis of four malignant cell lines Biomedicine & Pharmacotherapy 2007 61 6 366 369 10.1016/j.biopha.2007.02.015 2-s2.0-34547606014 17448625 source

      Not checked in the free run.

    • cites [11] Zefferino R. Leone A. Piccaluga S. Cincione R. Ambrosi L. Mercury modulates interplay between IL-1β, TNF-α, and gap junctional intercellular communication in keratinocytes: mitigation by lycopene Journal of Immunotoxicology 2008 5 4 353 360 10.1080/15476910802482854 2-s2.0-65249160572 19404869 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Cell culture studies are usually carried out under abnormal conditions known as "culture shock," where cells are exposed to high oxygen tension and free metal ions in the medium.

    “It is noteworthy that cell culture studies are usually carried out under abnormal conditions known as “culture shock,” where cells are exposed to high oxygen tension and to free metal ions in the medium [27, 55].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [27] Lin C.-Y. Huang C.-S. Hu M.-L. The use of fetal bovine serum as delivery vehicle to improve the uptake and stability of lycopene in cell culture studies British Journal of Nutrition 2007 98 1 226 232 10.1017/S0007114507691752 2-s2.0-34547970907 17367572 source

      Not checked in the free run.

    • cites [55] Halliwell B. Oxidative stress in cell culture: an under-appreciated problem? FEBS Letters 2003 540 1–3 3 6 10.1016/s0014-5793(03)00235-7 2-s2.0-0037430971 12681474 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Chemopreventive antioxidants can have a corrective activity as selective inducers of apoptosis in transformed cells.

    “Chemopreventive antioxidants are mostly studied for their role as radical scavengers, but this preventive role can be complemented by a corrective activity as selective inducers of apoptosis in transformed cells [12].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12] Brash D. E. Havre P. A. New careers for antioxidants Proceedings of the National Academy of Sciences of the United States of America 2002 99 22 13969 13971 10.1073/pnas.232574399 2-s2.0-0037195154 12391310 PMC137820 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Differences were considered statistically significant when P < 0.05.

    “The differences were considered statistically significant when P < 0.05.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The solution with the highest lycopene dose had a suitable osmolarity lower than 320 mOsm/kg (~268 mOsm/kg).

    “Furthermore, it should be also noted that the solution with the highest lycopene dose had a suitable osmolarity lower than 320 mOsm/kg (~268 mOsm/kg).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    HaCaT cell line is immortal (>140 passages) but remains nontumorigenic, and is aneuploid (hypotetraploid) with unique stable marker chromosomes indicating monoclonal origin.

    “This cell line is immortal (>140 passages) but remains nontumorigenic, and it is aneuploid (hypotetraploid) with unique stable marker chromosomes indicating monoclonal origin [40].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [40] Boukamp P. Petrussevska R. T. Breitkreutz D. Hornung J. Markham A. Fusenig N. E. Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line Journal of Cell Biology 1988 106 3 761 771 10.1083/jcb.106.3.761 2-s2.0-0023852747 2450098 PMC2115116 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The assays results were compared to CD aqueous solutions (vehicle control) with the same dilution factors used for complexed lycopene samples.

    “Besides the negative control (nonexposed and nonirradiated cells), the assays results were also compared to CD aqueous solutions (vehicle control) with the same dilution factors used for complexed lycopene samples.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    At low oxygen tension, lycopene can scavenge peroxyl radicals, inhibiting lipid peroxidation.

    “At low oxygen tension, it can also scavenge peroxyl radicals, inhibiting the process of lipid peroxidation [8].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [8] Stahl W. Sies H. Carotenoids and flavonoids contribute to nutritional protection against skin damage from sunlight Molecular Biotechnology 2007 37 1 26 30 10.1007/s12033-007-0051-z 2-s2.0-35848956087 17914160 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    HaCaT cells medium (DMEM) contains ferric nitrate and Fe(III) can react with excess neutral carotenoids such as lycopene.

    “In fact, the HaCaT cells medium (DMEM) contains ferric nitrate (Fe(NO3)3·9 H2O) and Fe(III) can react with excess neutral carotenoids, such as lycopene.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [58] Boon C. S. McClements D. J. Weiss J. Decker E. A. Role of iron and hydroperoxides in the degradation of lycopene in oil-in-water emulsions Journal of Agricultural and Food Chemistry 2009 57 7 2993 2998 10.1021/jf803747j 2-s2.0-64549108930 19265448 source

      Not checked in the free run.

    • cites [59] Boon C. S. McClements D. J. Weiss J. Decker E. A. Factors influencing the chemical stability of carotenoids in foods Critical Reviews in Food Science and Nutrition 2010 50 6 515 532 10.1080/10408390802565889 2-s2.0-77953194780 20544442 source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    The results are reported as mean ± SD of at least three replicates/treatment, and at least three independent assays were performed for each analysis.

    “The results are reported as mean ± SD of at least three replicates/treatment. In addition, at least three independent assays were performed for each analysis.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Lycopene is a powerful antioxidant both in vitro and in vivo against oxidation of proteins, lipids, and DNA, and one of the most potent scavengers of singlet oxygen free radicals among carotenoids.

    “Lycopene is a powerful antioxidant both in vitro and in vivo against the oxidation of proteins, lipids, and DNA, and it has been identified as one of the most potent scavengers of singlet species of oxygen free radicals—the highest among the carotenoids [6, 7].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [6] Dinkova-Kostova A. T. Phytochemicals as protectors against ultraviolet radiation: versatility of effects and mechanisms Planta Medica 2008 74 13 1548 1559 10.1055/s-2008-1081296 2-s2.0-56249104197 18696411 source

      Not checked in the free run.

    • cites [7] Mein J. R. Lian F. Wang X.-D. Biological activity of lycopene metabolites: implications for cancer prevention Nutrition Reviews 2008 66 12 667 683 10.1111/j.1753-4887.2008.00120.x 2-s2.0-60549109477 19019036 PMC6824483 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    Primer specificity was confirmed using the In-Silico PCR UCSC Genome Browser.

    “Primer design was performed using Primer3 [48] and primer specificity was confirmed using the In-Silico PCR UCSC Genome Browser [49].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [49] Kent J. UCSC in Silico PCR 2013 http://genome.ucsc.edu/cgi-bin/hgPcr?command=start

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Different half-life values of lycopene under standard cell culture are reported, for example, 12-20 h.

    “Different half-life values of lycopene under standard cell culture are reported in the literature, for example, 12–20 h [37].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [37] Cooney R. V. Kappock T. J. Pung A. Bertram J. S. Lester P. [6] Solubilization, cellular uptake, and activity of β-carotene and other carotenoids as inhibitors of neoplastic transformation in cultured cells Methods in Enzymology 1993 214 Academic Press 55 68 10.1016/0076-6879(93)14053-L 8469152

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    SDHA was used as the reference gene for qPCR.

    “SDHA (succinate dehydrogenase) was used as the reference gene.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Lycopene was reported as the most quickly depleted antioxidant in skin upon exposure to solar radiation and might play a role of protection against UVR.

    “Lycopene was reported as the most quickly depleted antioxidant in skin upon exposure to solar radiation [9] and might play a role of protection against UVR.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [9] Ribaya-Mercado J. D. Garmyn M. Gilchrest B. A. Russell R. M. Skin lycopene is destroyed preferentially over β-carotene during ultraviolet irradiation in humans The Journal of Nutrition 1995 125 7 1854 1859 2-s2.0-0028997258 7616301 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Depletion of cholesterol by methyl-β-cyclodextrin reduced Fas aggregation which was accompanied with a reduced apoptotic but increased nonapoptotic death of UV-B-irradiated HaCaT cells.

    “Depletion of cholesterol by methyl-β-cyclodextrin reduced Fas aggregation which was accompanied with a reduced apoptotic but increased nonapoptotic death of UV-B-irradiated HaCaT cells [73].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [73] George K. S. Elyassaki W. Wu Q. Wu S. The role of cholesterol in UV light B-induced apoptosis Photochemistry and Photobiology 2012 88 5 1191 1197 10.1111/j.1751-1097.2011.01038.x 2-s2.0-84865984241 22077874 PMC3297721 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Growth inhibition of lycopene on MCF-7 breast cancer cells is associated with decreased G1-S cell cycle progression, decreased cyclin D1 expression, and stabilization of p27 in the cyclin E-CDK complex.

    “It has been reported that the growth inhibition of lycopene on MCF-7 breast cancer cells was also associated with decreased G1-S cell cycle progression, decreased cyclin D1 expression, and stabilization of p27 in the cyclin E-CDK complex [7, 66].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [7] Mein J. R. Lian F. Wang X.-D. Biological activity of lycopene metabolites: implications for cancer prevention Nutrition Reviews 2008 66 12 667 683 10.1111/j.1753-4887.2008.00120.x 2-s2.0-60549109477 19019036 PMC6824483 source

      Not checked in the free run.

    • cites [66] Nahum A. Zeller L. Danilenko M. Lycopene inhibition of IGF-induced cancer cell growth depends on the level of cyclin D1 European Journal of Nutrition 2006 45 5 275 282 10.1007/s00394-006-0595-x 2-s2.0-33746773068 16565789 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Reagan-Shaw et al. obtained a significant decrease of SOD activity (MnSOD) after treatment with sanguinarine, enhancing UV-B-mediated oxidative stress in HaCaT cells.

    “Reagan-Shaw et al. [5] have also obtained a significant decrease of SOD activity (MnSOD) after treatment with sanguinarine, enhancing UV-B-mediated oxidative stress in HaCaT cells.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [5] Reagan-Shaw S. Breur J. Ahmad N. Enhancement of UVB radiation-mediated apoptosis by sanguinarine in HaCaT human immortalized keratinocytes Molecular Cancer Therapeutics 2006 5 2 418 429 10.1158/1535-7163.MCT-05-0250 2-s2.0-33644974099 16505117 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Methyl β-CD inhibits cell growth and induces cell cycle arrest via a prostaglandin E2 independent pathway in Raw264.7 macrophage cells.

    “it has been reported that methyl β-CD inhibits cell growth and induces cell cycle arrest via a prostaglandin E2 independent pathway in Raw264.7 macrophage cells [67].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [67] Choi Y.-A. Chin B. R. Rhee D. H. Methyl-β-cyclodextrin inhibits cell growth and cell cycle arrest via a prostaglandin E2 independent pathway Experimental and Molecular Medicine 2004 36 1 78 84 10.1038/emm.2004.11 2-s2.0-1642418262 15031675 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Nagao found that oxidized metabolites of lycopene but not lycopene itself can inhibit cell growth and stimulate apoptosis in HL-60.

    “Nagao [81] found that oxidized metabolites of lycopene but not lycopene itself can inhibit cell growth and stimulate apoptosis in a different cell line (HL-60).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [81] Nagao A. Oxidative conversion of carotenoids to retinoids and other products Journal of Nutrition 2004 134 1 237S 240S 2-s2.0-0347986905 14704326 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Cholesterol presence is essential for lipid raft formation and Fas-receptor activation, and this could inhibit UV-B induced apoptosis.

    “Cholesterol presence is essential for lipid raft formation and Fas-receptor activation, and this could inhibit UV-B induced apoptosis, as demonstrated by George et al. [73].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [73] George K. S. Elyassaki W. Wu Q. Wu S. The role of cholesterol in UV light B-induced apoptosis Photochemistry and Photobiology 2012 88 5 1191 1197 10.1111/j.1751-1097.2011.01038.x 2-s2.0-84865984241 22077874 PMC3297721 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Lycopene in human prostate cancer cells inhibited cell growth, but the oxidized mixtures displayed markedly more potent growth inhibition.

    “In another study, lycopene in human prostate cancer cells inhibited cell growth, but the oxidized mixtures displayed markedly more potent growth inhibition [81, 82].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [81] Nagao A. Oxidative conversion of carotenoids to retinoids and other products Journal of Nutrition 2004 134 1 237S 240S 2-s2.0-0347986905 14704326 source

      Not checked in the free run.

    • cites [82] Hantz H. L. Young L. F. Martin K. R. Physiologically attainable concentrations of lycopene induce mitochondrial apoptosis in LNCaP human prostate cancer cells Experimental Biology and Medicine 2005 230 3 171 179 2-s2.0-14344259481 15734720 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based). May combine two claims.

    Interpretationnone given

    These two biomarkers (BAX and caspase 3) were the most useful probably because those genes might be more involved in this process.

    “These two biomarkers were the most useful probably because those genes might be more involved in this process.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: UV-B irradiation increases levels of apoptosis biomarkers, especially the proapoptotic protein Bax, thereby inducing apoptosis in skin cells.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Cell cycle arrest increases the time available for DNA repair before its replication and mutation fixation processes.

    “Cell cycle arrest increases the time available for DNA repair before its replication and mutation fixation processes [5].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [5] Reagan-Shaw S. Breur J. Ahmad N. Enhancement of UVB radiation-mediated apoptosis by sanguinarine in HaCaT human immortalized keratinocytes Molecular Cancer Therapeutics 2006 5 2 418 429 10.1158/1535-7163.MCT-05-0250 2-s2.0-33644974099 16505117 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    UVR can cause cell cycle arrest both at G1 and G2 phases of cell cycle.

    “Previous studies have shown that UVR can cause cell cycle arrest both at G1 [63] and G2 phases [64] of cell cycle.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [63] Al-Mohanna M. A. Al-Khodairy F. M. Krezolek Z. Bertilsson P.-A. Al-Houssein A. Aboussekhra A. P53 is dispensable for UV-induced cell cycle arrest at late G1 in mammalian cells Carcinogenesis 2001 22 4 573 578 10.1093/carcin/22.4.573 2-s2.0-0035067274 11285191 source

      Not checked in the free run.

    • cites [64] Pavey S. Russell T. Gabrielli B. G2 phase cell cycle arrest in human skin following UV irradiation Oncogene 2001 20 43 6103 6110 10.1038/sj.onc.1204707 2-s2.0-0035959744 11593418 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Similar results were obtained by Reagan-Shaw et al. who suggested that sanguinarine may protect skin cells from UVB-mediated damage via apoptotic elimination of damaged cells that escaped from programmed cell death.

    “In general, similar results were obtained by Reagan-Shaw et al. [5] who suggested that sanguinarine (also a botanical antioxidant) may protect skin cells (also HaCaT cell line) from UVB-mediated damage via apoptotic elimination of damaged cells that escaped from the programmed cell death.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [5] Reagan-Shaw S. Breur J. Ahmad N. Enhancement of UVB radiation-mediated apoptosis by sanguinarine in HaCaT human immortalized keratinocytes Molecular Cancer Therapeutics 2006 5 2 418 429 10.1158/1535-7163.MCT-05-0250 2-s2.0-33644974099 16505117 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Complexed lycopene might play a corrective role or cytotoxic effect in photodamaged and preneoplastic keratinocytes, while allowing other keratinocytes to accelerate repairing mechanisms becoming viable.

    “Therefore, complexed lycopene might play a corrective role or cytotoxic effect in photodamaged and preneoplastic keratinocytes, while allowing other keratinocytes to accelerate repairing mechanisms becoming viable.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: UV-B irradiation increases levels of apoptosis biomarkers, especially the proapoptotic protein Bax, thereby inducing apoptosis in skin cells.
    • Rests on an assumption: Bcl-2 family proteins can modulate mitochondrial permeability through oxidative phosphorylation during apoptosis.
    • Rests on an assumption: UVR results in an increased generation of ROS that interacts with proteins, lipids, and DNA, overwhelming the antioxidant defense mechanisms of the cells.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    HaCaT cell line (which harbors two mutant p53 alleles) are more susceptible to apoptosis than normal keratinocytes in vitro.

    “Bowen et al. [68] have found that HaCaT cell line (which harbors two mutant p53 alleles) are more susceptible to apoptosis than normal keratinocytes in vitro”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [68] Bowen A. R. Hanks A. N. Allen S. M. Alexander A. Diedrich M. J. Grossman D. Apoptosis regulators and responses in human melanocytic and keratinocytic cells Journal of Investigative Dermatology 2003 120 1 48 55 10.1046/j.1523-1747.2003.12010.x 2-s2.0-0037244772 12535197 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    UV-B irradiation activates diverse cellular responses in human cells, such as cell cycle arrest, DNA repair, and apoptosis through signal transduction pathways.

    “UV-B irradiation activates diverse cellular responses in human cells, such as cell cycle arrest, DNA repair, and apoptosis through signal transduction pathways [15].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [15] Heffernan T. P. Kawasumi M. Blasina A. Anderes K. Conney A. H. Nghiem P. ATR-Chk1 pathway inhibition promotes apoptosis after UV treatment in primary human keratinocytes: potential basis for the UV protective effects of caffeine Journal of Investigative Dermatology 2009 129 7 1805 1815 10.1038/jid.2008.435 2-s2.0-67449110953 19242509 PMC2829385 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Changes in the Bax/Bcl-2 ratio suggest a corresponding change in mitochondrial permeability to release apoptogenic molecules from the mitochondria to the cytosol.

    “Changes in the Bax/Bcl-2 ratio suggest a corresponding change in mitochondrial permeability to release apoptogenic molecules from the mitochondria to the cytosol [5].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [5] Reagan-Shaw S. Breur J. Ahmad N. Enhancement of UVB radiation-mediated apoptosis by sanguinarine in HaCaT human immortalized keratinocytes Molecular Cancer Therapeutics 2006 5 2 418 429 10.1158/1535-7163.MCT-05-0250 2-s2.0-33644974099 16505117 source

      Not checked in the free run.

36 of 36

  • The authors state this as an assumption.

    For therapeutic purposes, lycopene would be applied topically.

    “Therefore, for therapeutic purposes (assuming topical application) we used a range above these normal plasma levels (5 up to 20 μM).”

  • The paper relies on this without support.

    UV-B irradiation increases levels of apoptosis biomarkers, especially the proapoptotic protein Bax, thereby inducing apoptosis in skin cells.

    “UV-B irradiation has been shown to increase levels of apoptosis biomarkers, especially the proapoptotic protein Bax, thereby inducing apoptosis in skin cells.”

  • The paper relies on this without support.

    Bcl-2 family proteins can modulate mitochondrial permeability through oxidative phosphorylation during apoptosis.

    “Bcl-2 family proteins can modulate mitochondrial permeability through oxidative phosphorylation during apoptosis.”

  • The paper relies on this without support.

    UVR results in an increased generation of ROS that interacts with proteins, lipids, and DNA, overwhelming the antioxidant defense mechanisms of the cells.

    “UVR results in an increased generation of ROS that interacts with proteins, lipids, and DNA, overwhelming the antioxidant defense mechanisms of the cells.”

  • The paper relies on this without support.

    Cyclin D regulates the transition from G0 to early G1 phase, while cyclin E regulates the transition of the cell from late G1 phase to S phase; p21 and p27 CDK inhibitors bind and inhibit the activity of cyclin E/CDK2 complex, blocking cell cycle progression in G1 phase.

    “Cyclin D regulates the transition from G0 to early G1 phase, while cyclin E regulates the transition of the cell from late G1 phase to S phase; p21 and p27 CDK inhibitors bind and inhibit the activity of cyclin E/CDK2 complex, blocking cell cycle progression in G1 phase.”

  • The paper relies on this without support.

    After UV irradiation, the half-life of the tumor suppressor (p53) appears to be extended which will induce the p21 CDK inhibitor leading to G1 phase arrest or cell death by apoptosis.

    “In fact, after UV irradiation, the half-life of the tumor suppressor (p53) appears to be extended which will induce the p21 CDK inhibitor leading to G1 phase arrest or cell death by apoptosis.”

  • The paper relies on this without support.

    CD can form complexes with lipids from the plasma membrane.

    “Moreover, since CD can form complexes with lipids from the plasma membrane, it might be possible that PS was shielded by CD against binding to Annexin V, a requirement for the validity of Annexin V assay.”
7 of 7

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?

  • Lycopene preexposure on UVB-irradiated human keratinocytes corrects injury in mild photodamaged cells and acts as a cytotoxic agent in preneoplastic cells.

    “Indeed, lycopene preexposure on UVB-irradiated human keratinocytes was found to play a diversified role in UVB-irradiated keratinocytes, depending on the level of damage, correcting the injury in mild photodamaged cells and acting as a cytotoxic agent in preneoplastic cells [110].”

    From Antioxidants from Plants Protect against Skin Photoaging (2018) · cites this paper as [110]

  • In irradiated keratinocytes, lycopene pretreatment resulted in overexpression of BAX gene, cell cycle delay at S-phase transition, and decrease of cells in G0/G1 phase.

    “In particular, in irradiated keratinocytes, lycopene pretreatment resulted in the overexpression of BAX gene, a cell cycle delay at S-phase transition, and in a consequent decrease of cells in G0/G1 phase [110].”

    From Antioxidants from Plants Protect against Skin Photoaging (2018) · cites this paper as [110]

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.

  • Nonirradiated ROS effect is described in opposite ways

    Minor

    The results state that lycopene did not increase ROS production in nonirradiated cells, while the conclusion says that the nontoxic dose slightly increased ROS content in those cells.

1 of 1

The citation lists haven’t been fetched yet

References 86 · Cited by 57

Research works printed but not linked: 4

  1. Souto E. B., 2007, Topical delivery of oily actives using solid lipid particles, Pharmaceutical Technology Europe, 19, 28
  2. Cooney R. V., 1993, Methods in Enzymology, 55
  3. Kent J., 2013, UCSC in Silico PCR
  4. Harang B., 2000, Composition Having Tanning and Photoprotective Activity, and Its Cosmetic Applications

Authors
Ascenso, A., Pedrosa, T., Pinho, S., Pinho, F., Oliveira, J. M. P. F. D., Cabral Marques, H., Oliveira, H., Simões, S., & Santos, C.
Affiliations
  • University of Lisbon (PT)
  • University of Aveiro (PT)
Corresponding author
Ascenso, Andreia
ORCID
Venue
Oxidative Medicine and Cellular Longevity
Publisher
Wiley
Published
2015-11-17
Volume
2016
Issue
1
Pages
8214631-8214631
ISSN
  • 1942-0994 (ISSN-L)
  • 1942-0900
DOI
10.1155/2016/8214631
PMC
PMC4664803
OpenAlex
W1615669455
Semantic Scholar
f998390356a883d0185b97845b97983098fb1bf0
Cited by
57
References
86
Citations by year
2026: 1 · 2025: 5 · 2024: 3 · 2023: 9 · 2022: 2 · 2021: 9 · 2020: 5 · 2019: 9 · 2018: 5 · 2017: 7 · 2016: 1 · 2013: 1
FWCI
4.84
Type
journal article
Language
en
Open access
Licence
Locations
  • Oxidative Medicine and Cellular Longevity (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • European Regional Development Fund (PEst-OE/SAU/UI4013/2011, UID/AMB/50017/2013., SFRH/BPD/48853/2008, FRH/BPD/74868/2010)
  • Foundation for Science and Technology (PEst-OE/SAU/UI4013/2011, UID/AMB/50017/2013., SFRH/BPD/48853/2008, FRH/BPD/74868/2010)
  • Fundação para a Ciência e a Tecnologia (PEst-OE/SAU/UI4013/2011, UID/AMB/50017/2013., SFRH/BPD/48853/2008, FRH/BPD/74868/2010)
Topics
  • Health Sciences › Medicine › Dermatology › Skin Protection and Aging
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
Keywords
lycopene, UVB irradiation, human keratinocytes, photoprotection, genotoxicity, clastogenicity, apoptosis, Bax gene expression, cell cycle arrest, oxidative stress, reactive oxygen species, skin cancer prevention, antioxidant depletion
MeSH terms
Lycopene, Carotenoids, Cell Cycle, Cell Line, Humans, Skin Neoplasms, Ultraviolet Rays, Keratinocytes, Apoptosis, Reactive Oxygen Species, bcl-2-Associated X Protein

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

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