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Cited by 33Wound Healing and TreatmentsSkin Protection and AgingTrace Elements in Health

Skin Regenerative and Anti-Cancer Actions of Copper Peptides

Open access
Pickart, Loren, Margolina, Anna·2018·Cosmetics
DOI 10.3390/cosmetics5020029
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Abstract

Topical remedies capable of protecting skin from damage and supporting its regeneration can improve skin’s health as well as its appearance. Small copper peptides have an excellent safety record and are widely used in cosmetic products. The most studied copper peptide is GHK-Cu (glycyl-L-histidyl-L-lysine), a small copper-binding peptide, naturally present in human plasma. Since its discovery in 1973, in vivo and in vitro studies have shown that GHK-Cu possesses a wealth of health-positive actions including improving wound contraction and epithelization, and increasing the production of growth factors and activity of antioxidant enzymes. Recently, gene expression profiling shed new light on diverse biological actions of GHK-Cu. The present paper discusses evidence of GHK-Cu and other small copper peptides possessing potent anti-cancer properties.

AI snapshot

Written from the paper’s full text.

TL;DR

This narrative review argues that small copper peptides, especially GHK-Cu, have skin-regenerative and anti-cancer actions, largely by modulating gene expression. It summarizes preclinical, gene-profiling, antioxidant, anti-inflammatory, and DNA-repair evidence, while noting that clinical studies are still needed.

Key findings

  • GHK-Cu is a naturally occurring copper-binding tripeptide with wound-healing and skin-regenerative actions; Broad Institute gene-expression data indicate GHK affects 31.2% of human genes by ≥50%, stimulating 59% and suppressing 41% of those genes.
  • GHK upregulates apoptosis and cancer-suppressor genes, including CASP1 (+432%), USP29 (+1056%), IFNA21 (+955%), TP73 (+938%), PTEN (+165%), and BRCA1 (+44%), and downregulates cancer enhancers such as ABCB1 (−1537%), STAT5 (−982%), FGFR2 (−904%), and FAIM2 (−749%); DNA-repair genes showed 47 UP and 5 DOWN, including PARP3 (+253%), POLM (+225%), and RAD50 (+175%).
  • Preclinical anti-cancer evidence includes GHK/GHK-PEG reactivating apoptosis at 1–10 nanomolar and inhibiting human SH-SY5Y neuroblastoma and U937 histiocytic lymphoma cells while increasing NIH3T3 fibroblast replication; GHK-Cu plus ascorbic acid suppressed mouse sarcoma 180, and Pauling’s Gly-Gly-His–copper system inhibited Ehrlich ascites tumor cells in mice.
  • Antioxidant/anti-inflammatory findings include GHK protecting cultured skin keratinocytes at 20 mg/mL or 0.2%, GHK-Cu producing 87% inhibition of iron release from ferritin, and GHK-Cu reducing ROS, TNF-α, and IL-6 in cited models.

Methods

  • Narrative review; no systematic review, meta-analysis, or formal clinical trial is described.
  • Synthesizes in vitro and in vivo studies plus gene-expression profiling: the Broad Institute measured GHK effects on 13,424 genes, yielding 4,192 genes with ±50% changes; CMap was used to select GHK and securinine from 1,309 bioactive compounds for metastatic colon cancer analysis.
  • Gene-expression tables summarize changes in apoptosis, cancer-suppressor, cancer-enhancer, DNA-repair, and antioxidant genes.

Limitations

  • The paper states no formal limitations and declares no conflict of interest; however, the authors mention filing and issuing patents on copper peptides as anti-cancer actives (e.g., U.S. Patent 9,586,989), an evident potential conflict of interest.
  • Evident: anti-cancer conclusions rely largely on preclinical cell/animal and gene-expression data; the paper itself says “the time has come for conducting actual clinical studies,” indicating no clinical trials are reported.
  • Evident: the review is non-systematic and does not report risk-of-bias assessment, clinical endpoints, or independent replication.

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

Integrity signals

Registry

Crossref · 10.3390/cosmetics5020029

Cites

46 of 47 references verified0 citation errors · 1 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 88 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Copper 2+ is necessary for most GHK effects.

    “There are experiments that use copper-free GHK with successful results but all of our studies indicated copper 2+ is necessary for most GHK effects.”
    Quote in the paperSubstantial claim
  • Findingcitation

    The copper chelator bathocuproine abolishes GHK actions.

    “The copper chelator bathocuproine abolishes GHK actions.”
    Quote in the paperSubstantial claim
  • Findingcitation

    GHK induced gene expression changes including 84 cancer or growth inhibitory genes.

    “In 2014, using the Broad Institute CMap, Pickart et al. found gene expression changes induced by GHK.This included 84 cancer or growth inhibitory genes.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [24] Pickart, 2014, GHK, the human skin remodeling peptide, induces anti-cancer expression of numerous caspase, growth regulatory, and DNA repair genes, J. Anal. Oncol.

      Not checked in the free run.

  • Findingown data

    GHK stimulates gene expression for DNA repair genes (47 UP, 5 DOWN).

    “In our work with the Broad Institute CMap, we found that GHK stimulates gene expression for DNA Repair genes (47 UP, 5 DOWN).”
    Quote in the paperSubstantial claim
  • Findingcitation

    GHK increased CASP8 expression by 399%.

    “CASP 8 399”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Pickart, 2014, GHK, the human skin remodeling peptide, induces anti-cancer expression of numerous caspase, growth regulatory, and DNA repair genes, J. Anal. Oncol.

      Not checked in the free run.

  • May combine two claims. 20
  • Classified as probably not a substantial claim. 28
  • The quote only partly states this claim. 11

  • May combine two claims.

    Findingcitation

    GHK stimulates or suppresses 31.2% of human genes with a change of 50% or more, stimulating 59% of the genes and suppressing 41%.

    “According to the Broad Institute data, GHK stimulates or suppresses 31.2% of human genes with a change of 50% or more (stimulating 59% of the genes and suppressing 41%) [11].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [11] Campbell, 2012, A gene expression signature of emphysema-related lung destruction and its reversal by the tripeptide GHK, Genome Med.

      Not checked in the free run.

  • May combine two claims.

    Findingreasoning

    GHK-Cu up- and down-regulates a significant number of human genes, essentially resetting the human genome back to health.

    “This led to consecutive studies, which confirmed that GHK-Cu is able to up-and down-regulate a significant number of human genes, essentially resetting the human genome back to health (see Table 1).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Findingcitation

    GHK increased CASP1 expression by 432%.

    “CASP 1 432”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Pickart, 2014, GHK, the human skin remodeling peptide, induces anti-cancer expression of numerous caspase, growth regulatory, and DNA repair genes, J. Anal. Oncol.

      Not checked in the free run.

  • The quote only partly states this claim.

    Findingcitation

    GHK decreased ABCB1 expression by 1537%.

    “ABCB1 -1537”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Pickart, 2014, GHK, the human skin remodeling peptide, induces anti-cancer expression of numerous caspase, growth regulatory, and DNA repair genes, J. Anal. Oncol.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing), S4 (based).

    Findingcitation

    GHK increased PTEN expression by 165%.

    “PTEN 165”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Pickart, 2014, GHK, the human skin remodeling peptide, induces anti-cancer expression of numerous caspase, growth regulatory, and DNA repair genes, J. Anal. Oncol.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing), S4 (based).

    Findingcitation

    GHK increased NRG1 expression by 164%.

    “NRG1 164”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Pickart, 2014, GHK, the human skin remodeling peptide, induces anti-cancer expression of numerous caspase, growth regulatory, and DNA repair genes, J. Anal. Oncol.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing), S4 (based).

    Findingcitation

    GHK increased CASP10 expression by 195%.

    “CASP 10 195”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Pickart, 2014, GHK, the human skin remodeling peptide, induces anti-cancer expression of numerous caspase, growth regulatory, and DNA repair genes, J. Anal. Oncol.

      Not checked in the free run.

  • The quote only partly states this claim.

    Findingcitation

    GHK increased ITGB4 expression by 609%.

    “ITGB4 609”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Pickart, 2014, GHK, the human skin remodeling peptide, induces anti-cancer expression of numerous caspase, growth regulatory, and DNA repair genes, J. Anal. Oncol.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing), S4 (based).

    Findingcitation

    GHK increased IL25 expression by 891%.

    “IL25 891”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Pickart, 2014, GHK, the human skin remodeling peptide, induces anti-cancer expression of numerous caspase, growth regulatory, and DNA repair genes, J. Anal. Oncol.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing), S4 (based).

    Findingcitation

    GHK increased TP73 expression by 938%.

    “TP73 938”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Pickart, 2014, GHK, the human skin remodeling peptide, induces anti-cancer expression of numerous caspase, growth regulatory, and DNA repair genes, J. Anal. Oncol.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing), S4 (based).

    Findingcitation

    GHK increased IL15 expression by 875%.

    “IL15 875”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Pickart, 2014, GHK, the human skin remodeling peptide, induces anti-cancer expression of numerous caspase, growth regulatory, and DNA repair genes, J. Anal. Oncol.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing), S4 (based). The quote only partly states this claim.

    Findingcitation

    GHK increased BRCA1 expression by 44%.

    “BRCA 1 * 44”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Pickart, 2014, GHK, the human skin remodeling peptide, induces anti-cancer expression of numerous caspase, growth regulatory, and DNA repair genes, J. Anal. Oncol.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing), S4 (based).

    Findingcitation

    GHK increased USP29 expression by 1056%.

    “USP 29 1056”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Pickart, 2014, GHK, the human skin remodeling peptide, induces anti-cancer expression of numerous caspase, growth regulatory, and DNA repair genes, J. Anal. Oncol.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing), S4 (based).

    Findingcitation

    GHK increased DCN expression by 44%.

    “DCN * 44”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Pickart, 2014, GHK, the human skin remodeling peptide, induces anti-cancer expression of numerous caspase, growth regulatory, and DNA repair genes, J. Anal. Oncol.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing), S4 (based). The quote only partly states this claim.

    Findingcitation

    GHK increased ATM expression by 107%.

    “ATM 107”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Pickart, 2014, GHK, the human skin remodeling peptide, induces anti-cancer expression of numerous caspase, growth regulatory, and DNA repair genes, J. Anal. Oncol.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). The quote only partly states this claim.

    Findingcitation

    GHK increased IFNA21 expression by 955%.

    “IFNA 21 955”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Pickart, 2014, GHK, the human skin remodeling peptide, induces anti-cancer expression of numerous caspase, growth regulatory, and DNA repair genes, J. Anal. Oncol.

      Not checked in the free run.

  • The quote only partly states this claim.

    Findingcitation

    GHK increased CARD10 expression by 173%.

    “CARD10 173”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Pickart, 2014, GHK, the human skin remodeling peptide, induces anti-cancer expression of numerous caspase, growth regulatory, and DNA repair genes, J. Anal. Oncol.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). The quote only partly states this claim.

    Findingcitation

    GHK increased ING2 expression by 337%.

    “ING2 337”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Pickart, 2014, GHK, the human skin remodeling peptide, induces anti-cancer expression of numerous caspase, growth regulatory, and DNA repair genes, J. Anal. Oncol.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). The quote only partly states this claim.

    Findingcitation

    GHK decreased FAIM2 expression by 749%.

    “FAIM2 -749”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Pickart, 2014, GHK, the human skin remodeling peptide, induces anti-cancer expression of numerous caspase, growth regulatory, and DNA repair genes, J. Anal. Oncol.

      Not checked in the free run.

  • The quote only partly states this claim.

    Findingcitation

    GHK increased RARA expression by 123%.

    “RARA | 123”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Pickart, 2014, GHK, the human skin remodeling peptide, induces anti-cancer expression of numerous caspase, growth regulatory, and DNA repair genes, J. Anal. Oncol.

      Not checked in the free run.

  • The quote only partly states this claim.

    Findingcitation

    GHK decreased FGFR2 expression by 904%.

    “FGFR2 -904”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Pickart, 2014, GHK, the human skin remodeling peptide, induces anti-cancer expression of numerous caspase, growth regulatory, and DNA repair genes, J. Anal. Oncol.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Findingcitation

    GHK decreased STAT5 expression by 982%.

    “STAT5 -982”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Pickart, 2014, GHK, the human skin remodeling peptide, induces anti-cancer expression of numerous caspase, growth regulatory, and DNA repair genes, J. Anal. Oncol.

      Not checked in the free run.

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

    Findingcitation

    GHK increased APOM expression by 403%.

    “APOM 403”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Pickart, 2014, GHK, the human skin remodeling peptide, induces anti-cancer expression of numerous caspase, growth regulatory, and DNA repair genes, J. Anal. Oncol.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing).

    Findingcitation

    GHK increased PTGS2 expression by 120%.

    “PTGS2 120”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Pickart, 2014, GHK, the human skin remodeling peptide, induces anti-cancer expression of numerous caspase, growth regulatory, and DNA repair genes, J. Anal. Oncol.

      Not checked in the free run.

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

    Findingcitation

    GHK increased MT3 expression by 142%.

    “MT3 142”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Pickart, 2014, GHK, the human skin remodeling peptide, induces anti-cancer expression of numerous caspase, growth regulatory, and DNA repair genes, J. Anal. Oncol.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing), S4 (based).

    Findingcitation

    GHK increased SLC2A9 expression by 117%.

    “SLC2A9 117”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Pickart, 2014, GHK, the human skin remodeling peptide, induces anti-cancer expression of numerous caspase, growth regulatory, and DNA repair genes, J. Anal. Oncol.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing).

    Findingcitation

    GHK increased GPSM3 expression by 193%.

    “GPSM3 193”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Pickart, 2014, GHK, the human skin remodeling peptide, induces anti-cancer expression of numerous caspase, growth regulatory, and DNA repair genes, J. Anal. Oncol.

      Not checked in the free run.

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

    Findingcitation

    GHK increased IL18BP expression by 295%.

    “IL18BP 295”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Pickart, 2014, GHK, the human skin remodeling peptide, induces anti-cancer expression of numerous caspase, growth regulatory, and DNA repair genes, J. Anal. Oncol.

      Not checked in the free run.

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

    Findingcitation

    GHK increased PON3 expression by 319%.

    “PON3 319”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Pickart, 2014, GHK, the human skin remodeling peptide, induces anti-cancer expression of numerous caspase, growth regulatory, and DNA repair genes, J. Anal. Oncol.

      Not checked in the free run.

  • The quote only partly states this claim.

    Findingcitation

    GHK decreased IL17A expression by 1018%.

    “IL17A -1018”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Pickart, 2014, GHK, the human skin remodeling peptide, induces anti-cancer expression of numerous caspase, growth regulatory, and DNA repair genes, J. Anal. Oncol.

      Not checked in the free run.

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

    Findingcitation

    GHK increased FABP1 expression by 186%.

    “FABP1 186”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Pickart, 2014, GHK, the human skin remodeling peptide, induces anti-cancer expression of numerous caspase, growth regulatory, and DNA repair genes, J. Anal. Oncol.

      Not checked in the free run.

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

    Premisecitation

    GHK-Cu is naturally present in human plasma.

    “The most studied copper peptide is GHK-Cu (glycyl-L-histidyl-L-lysine), a small copper-binding peptide, naturally present in human plasma.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [5] Pickart, 2008, The human tri-peptide GHK and tissue remodeling, J. Biomater. Sci. Polym. Ed. source

      Not checked in the free run.

    • cites [6] Pickart, L. (1973). A Tripeptide from Human Serum Which Enhances the Growth of Neoplastic Hepatocytes and the Survival of Normal Hepatocytes. [Ph.D. Thesis, University of California].

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Small copper peptides have an excellent safety record and are widely used in cosmetic products.

    “Small copper peptides have an excellent safety record and are widely used in cosmetic products.”
    • Also stated in: § 1. Introduction · plain
      “Such peptides have an excellent safety profile and can heal wounds, improve the condition of skin, and increase hair growth in young mice [1].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] Pickart, L. (1999). Tissue Protective and Regenerative Compositions. (5,888,522), U.S. Patent.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    GHK-Cu greatly improves conditions of aging skin by reducing wrinkles and sagging skin, reducing pigmentation, and stimulating collagen, elastin, and glycosaminoglycans.

    “It has been shown to greatly improve conditions of aging skin-reducing wrinkles and sagging skin, reducing pigmentation, and stimulating collagen, elastin, and glycosaminoglycans [4].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [4] Elsner, P., and Maibach, H.I. (2005). Copper Peptide and Skin. Cosmeceuticals and Active Cosmetics: Drugs vs. Cosmetics, Marcel Dekker. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    GHK is naturally present in human blood and declines with age.

    “GHK, which is naturally present in human blood, declines with age.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [7] Farage, M.A., Miller, K.W., and Maibach, H.I. (2017). Resetting Skin Genome Back to Health Naturally with GHK. Textbook of Aging Skin, Springer. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Copper peptides can heal wounds, improve skin condition, and increase hair growth in young mice.

    “Such peptides have an excellent safety profile and can heal wounds, improve the condition of skin, and increase hair growth in young mice [1].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] Pickart, L. (1999). Tissue Protective and Regenerative Compositions. (5,888,522), U.S. Patent.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A copper-binding peptide (Gly-Gly-His) with copper 2+ oxidizes ascorbic acid and kills cancer cells in cell culture.

    “In 1983, Linus Pauling and his group theorized that a copper-binding peptide (Gly-Gly-His) with copper 2+ would oxidize ascorbic acid and kill cancer cells.This approach did work in cell culture.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [21] Kimoto, 1983, Enhancement of antitumor activity of ascorbate against Ehrlich ascites tumor cells by the copper: Glycylglycylhistidine complex, Cancer Res.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    GHK reverses damage and stimulates regeneration in COPD lung tissue by reversing gene expression associated with emphysema-related lung destruction.

    “In 2012, GHK was found to reverse damage and stimulate regeneration in COPD (chronic obstructive lung disease) lung tissue by reversing gene expression associated with emphysema-related lung destruction [10].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [10] Peled, T., Fibach, E., and Treves, A. (2005). Methods of Controlling Proliferation and Differentiation of Stem and Progenitor Cells. (6,962,698), U.S. Patent.

      Not checked in the free run.

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

    Premisecitation

    Diet, moderate wine consumption, and meditation have positive effects on gene expression.

    “Other studies showed positive effects of diet, moderate wine consumption, and meditation [14,15].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [14] McMurry, 2017, GHK-Cu Elicits in vitro, Dose-Dependent Transcriptional Alterations in Pathways Relevant to Extracellular Matrix Composition, Am. Thorac. Soc.

      Not checked in the free run.

    • cites [15] Declerck, 2015, From inflammaging to healthy aging by dietary lifestyle choices: Is epigenetics the key to personalized nutrition?, Clin. Epigenetics source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    GHK has extensive actions on gene expression relevant to tissue repair and induces dose-response gene expression on 329 genes associated with extracellular matrix composition in fetal lung fibroblasts.

    “In addition, a study that used fetal lung fibroblasts also found GHK to have extensive actions of gene expression relevant to tissue repair and induced dose-response gene expression on 329 genes associated with extracellular matrix composition [13].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [13] Pickart, L., Vasquez-Soltero, J.M., and Margolina, A. (2015). GHK Peptide as a Natural Modulator of Multiple Cellular Pathways in Skin Regeneration. Biomed Res. Int., 2015. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Age-related changes in gene expression are not permanent and can be reversed.

    “The fact that GHK has gene-modulating effects is important, because as science has now demonstrated, age-related changes in gene expression are not permanent and can be reversed.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [14] McMurry, 2017, GHK-Cu Elicits in vitro, Dose-Dependent Transcriptional Alterations in Pathways Relevant to Extracellular Matrix Composition, Am. Thorac. Soc.

      Not checked in the free run.

    • cites [15] Declerck, 2015, From inflammaging to healthy aging by dietary lifestyle choices: Is epigenetics the key to personalized nutrition?, Clin. Epigenetics source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    GHK stimulates hair growth and improves outcomes in hair grafting.

    “GHK stimulates hair growth and is used to improve outcomes in hair grafting [7].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [7] Farage, M.A., Miller, K.W., and Maibach, H.I. (2017). Resetting Skin Genome Back to Health Naturally with GHK. Textbook of Aging Skin, Springer. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    PDGF and TGF stimulate and perhaps help induce cancers.

    “However, both compounds were later found to stimulate, and perhaps help induce, cancers [16][17][18][19][20].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [16][17][18][19][20]

      Not checked in the free run.

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

    Premisecitation

    Physical exercise for 30 min a day, three times a week can revert gene expression in mitochondrial human DNA in older humans to a gene expression more like that of a younger person.

    “Recent studies have demonstrated that physical exercise for 30 min a day, three times a week can revert gene expression in mitochondrial human DNA in older humans to a gene expression that is more like that of a younger person.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [14] McMurry, 2017, GHK-Cu Elicits in vitro, Dose-Dependent Transcriptional Alterations in Pathways Relevant to Extracellular Matrix Composition, Am. Thorac. Soc.

      Not checked in the free run.

    • cites [15] Declerck, 2015, From inflammaging to healthy aging by dietary lifestyle choices: Is epigenetics the key to personalized nutrition?, Clin. Epigenetics source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    The anti-cancer activities of the Gly-Gly-His copper peptide in mice were due to the copper peptide and not to an interaction with ascorbic acid.

    “The Pauling group concluded that the anti-cancer activities were due to the copper peptide and not to an interaction with ascorbic acid [21].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [21] Kimoto, 1983, Enhancement of antitumor activity of ascorbate against Ehrlich ascites tumor cells by the copper: Glycylglycylhistidine complex, Cancer Res.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    GHK and securinine promote wound healing, extracellular remodeling, and macrophage activation.

    “Both GHK and securinine promote wound healing, extracellular remodeling, and macrophage activation [22].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [22] Hong, 2010, A “metastasis-prone” signature for early-stage mismatch-repair proficient sporadic colorectal cancer patients and its implications for possible therapeutics, Clin. Exp. Metastasis source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    GHK or GHK-PEG reactivated apoptosis at 1 to 10 nanomolar and inhibited cell growth of human SH-SY5Y neuroblastoma cells and human U937 histiocytic lymphoma cells.

    “Matalka et al. reported that GHK or GHK-PEG (GHK-Polyethylene glycol) both reactivated apoptosis at 1 to 10 nanomolar and inhibited cell growth of human SH-SY5Y neuroblastoma cells and human U937 histiocytic lymphoma cells.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [23] Matalka, 2012, The Tripeptide, GHK, Induces Programmed Cell Death in SH-SY5Y Neuroblastoma Cells, J. Biotechnol. Biomater. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    Stimulation of DNA repair genes may explain the observed positive effects of GHK-Cu on irradiated fibroblasts.

    “Since one of the effects of radiation is DNA damage, stimulation of DNA repair genes may explain the observed positive effects on irradiated fibroblasts.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Gene expression changes induced by GHK in vitro translate to functional anti-cancer effects in humans.

  • May combine two claims.

    Premisecitation

    In dermal fibroblasts, GHK and its copper complexes decreased IGF-2-dependent TGF-β1 secretion and decreased TNF-alpha dependent secretion of IL-6.

    “In dermal fibroblasts, GHK and its copper complexes decreased IGF-2-dependent TGF-β1 secretion as well as decreased TNF-alpha dependent secretion of IL-6, thus reducing inflammation [35,36].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [35] Gruchlik, 2014, Effect of GLY-HIS-LYS and its copper complex on TGF-β secretion in normal human dermal fibroblasts, Acta Pol. Pharm.

      Not checked in the free run.

    • cites [36] Gruchlik, 2012, Effect of Gly-Gly-His, Gly-His-Lys and their copper complexes on TNF-alpha-dependent IL-6 secretion in normal human dermal fibroblasts, Acta Pol. Pharm.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    GHK-Cu reduced Reactive Oxygen Species, increased superoxide dismutase activity, and decreased TNF-1 and IL-6 production in lipopolysaccharide-induced macrophages and in vivo.

    “In lipopolysaccharide-induced macrophages and in vivo, GHK-Cu reduced Reactive Oxygen Species (ROS), increased superoxide dismutase (SOD) activity, and decreased TNF-1 and IL-6 production.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [37] Park, 2016, The tri-peptide GHK-Cu complex ameliorates lipopolysaccharide-induced acute lung injury in mice, Oncotarget source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    GHK-Cu elevates the level of antioxidant enzymes in dermal wounds in rabbits and increases expression of antioxidant enzymes in diabetic wounds in rats, resulting in higher levels of antioxidants such as glutathione and ascorbic acid.

    “GHK-Cu was also found to elevate the level of antioxidant enzymes in the dermal wounds in rabbits and increase expression of antioxidant enzymes in diabetic wounds in rats, resulting in a higher level of antioxidants such as glutathione and ascorbic acid [45][46][47].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [45][46][47]

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    GHK reduced inflammatory cell infiltration and TNF-α and IL-6 expression in bronchoalveolar lavage fluid and MPO in lung extracts.

    “GHK reduced inflammatory cells infiltration and TNF-α and IL-6 expression in bronchoalveolar lavage fluid (BALF) and MPO in lung extracts [34].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [34] Zhou, 2017, GHK Peptide Inhibits Bleomycin-Induced Pulmonary Fibrosis in Mice by Suppressing TGFβ1/Smad-Mediated Epithelial-to-Mesenchymal Transition, Front. Pharmacol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    GHK prevented oxidation of low-density lipoproteins induced by copper ions and was more effective than superoxide dismutase (SOD1), which blocked only 20% of oxidation.

    “GHK prevented oxidation of low-density lipoproteins induced by copper ions and was more effective than superoxide dismutase (SOD1), which blocked only 20% of oxidation [41].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [41] Thomas, 1992, The influence of medium components on Cu(2+)-dependent oxidation of low-density lipoproteins and its sensitivity to superoxide dismutase, Biochim. Biophys. Acta source

      Not checked in the free run.

53 of 53

  • The paper relies on this without support.

    Gene expression changes induced by GHK in vitro translate to functional anti-cancer effects in humans.

    “This suggests a positive effect on DNA repair systems.”

  • The paper relies on this without support.

    Reactive oxygen species and other free radicals can accelerate skin aging and cause skin cancer.

    “Among factors that can accelerate skin aging and cause skin cancer are reactive oxygen species, and other types of free radicals, which can trigger oxidative processes and lead to DNA damage.”

  • The paper relies on this without support.

    The functions assigned to genes by the NCBI GENE database accurately reflect their roles in cancer and skin biology.

    “The names of the proteins and their functions are obtained from the NCBI GENE database.”
3 of 3

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?

  • GHK accelerates wound healing, helps restore normal tissue architecture through regulation of tissue remodeling, reduces inflammation and improves antioxidant defense.

    “It's been established in a number of studies that GHK accelerates wound healing, helps restore normal tissue architecture through regulation of tissue remodeling, reduces inflammation and improves antioxidant defense [9].”

    From Modulation of Gene Expression in Human Breast Cancer MCF7 and Prostate Cancer PC3 Cells by the Human Copper-Binding Peptide GHK-Cu (2021) · cites this paper as [9]

  • Copper ions are commonly included in cosmetics, and copper is used as an active component of face creams, including those for the care of mature, tired, dull or oily skin.

    “Copper ions are commonly included in cosmetics. Cu is used as an active component of face creams, including those for the care of mature, tired, dull or oily skin [118,130].”

    From Bioactive Compounds for Skin Health: A Review (2021) · cites this paper as [130]

  • The copper tripeptide complex (GHK-Cu and GSH-Cu) plays an important role in the protection and regeneration of skin tissue, increases the synthesis of collagen and elastin, and improves the condition of ageing skin.

    “The copper tripeptide complex (GHK-Cu and GSH-Cu) plays an important role in the protection and regeneration of skin tissue, increases the synthesis of collagen and elastin, and improves the condition of ageing skin.”

    From Bioactive Compounds for Skin Health: A Review (2021) · cites this paper as [130]

Cites

Flagged first, then by citations

Research works printed but not linked: 4

  1. Pickart, 2012, Anti-Aging Activity of the GHK Peptide—The skin and beyond, J. Aging. Res. Clin. Pract., 1, 13
  2. Pickart, L. (1973). A Tripeptide from Human Serum Which Enhances the Growth of Neoplastic Hepatocytes and the Survival of Normal Hepatocytes. [Ph.D. Thesis, University of California].
  3. McMurry, 2017, GHK-Cu Elicits in vitro, Dose-Dependent Transcriptional Alterations in Pathways Relevant to Extracellular Matrix Composition, Am. Thorac. Soc., A73, A2446
  4. Cherdakov, 2010, Synergetic antioxidant and reparative action of thymogen, dalargin and peptide Gly-His-Lys in tubular bone fractures, Exp. Biol. Med., 4, 15

Cited by

Sorted by citations

Related

Authors
Pickart, L., & Margolina, A.
Affiliations
Skin Biology, 4122 Factoria Boulevard SE, Suite Number 200, Bellevue, WA 98006, USA
Corresponding author
Pickart, Loren
ORCID
Venue
Cosmetics
Publisher
MDPI AG
Published
2018-04-21
Volume
5
Issue
2
Pages
29
ISSN
2079-9284 (ISSN-L)
DOI
10.3390/cosmetics5020029
OpenAlex
W2801658656
Semantic Scholar
b8b794d08683d51355b245d0705e19b51648c721
Cited by
33
References
46
Citations by year
2026: 9 · 2025: 7 · 2024: 4 · 2023: 4 · 2022: 2 · 2021: 3 · 2020: 1 · 2019: 3
FWCI
1.50
Type
journal article
Language
en
Open access
Licence
Locations
  • Cosmetics (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
  • Health Sciences › Medicine › Dermatology › Skin Protection and Aging
  • Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
Keywords
copper peptides, GHK-Cu, skin regeneration, anticancer activity, wound healing, re-epithelialization, growth factors, antioxidant enzymes, gene expression profiling, cosmetic ingredients, copper-binding peptides

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