GHK, the human skin remodeling peptide, induces anti-cancer expression of numerous caspase, growth regulatory, and DNA repair genes

Journal of Analytical Oncology

Volumn 3, Issue 2, 2014, Pages 79-87

  Pickart, Loren ^a   Vasquez Soltero, Jessica M ^a   Pickart, Francoise D ^a   Majnarich, John ^b  

^a Skin Biology Inc   (United States)

^b BioAnalysts Incorporated   (United States)

Author keywords

Cancer inhibition; Cancer therapy; Connectivity map; Copper peptides; Sarcoma

Indexed keywords

EID: 84901800410     PISSN: 19277210     EISSN: 19277229     Source Type: Journal    
DOI: 10.6000/1927-7229.2014.03.02.2     Document Type: Article

References (56)

1. Kheirelseid EA, Miller N, Chang KH, Nugent M, Kerin MJ. Clinical applications of gene expression in colorectal cancer. J Gastrointest Oncol 2013; 4: 144-57. http://dx.doi.org/10.3978/j.issn.2078-6891.2013.010
2. Claerhout S, Lim JY, Choi W, et al. Gene expression signature analysis identifies vorinostat as a candidate therapy for gastric cancer. PLoS One 2011; 6: e24662. http://dx.doi.org/10.1371/journal.pone.0024662
3. Pickart L, Freedman JH, Loker WJ, et al. Growth-modulating plasma tripeptide may function by facilitating copper uptake into cells. Nature 1980; 288: 715-7. http://dx.doi.org/10.1038/288715a0
4. Pickart L. The human tri-peptide GHK and tissue remodeling. J Biomater Sci Polym Ed 2008; 19: 969-88. http://dx.doi.org/10.1163/156856208784909435
5. Pickart L. The human tripeptide GHK (glycyl-l-histidyl-llysine), the copper switch, and the treatment of the degenerative conditions of aging. In: Klatz R, Goldman R, editors. Proceedings of the Anti-Aging Therapeutics XI; 2009: Chicago, Illinois: American Academy of Anti-Aging Medicine; 2009: p. 301-12.
6. Pickart L, Margolina A. Anti-aging activity of the GHK peptide-the skin and beyond. J Aging Res Clin Pr 2012; 1: 13-6.
7. Pickart L, Vasquez-Soltero JM, Margolina A. The human tripeptide GHK-Cu in prevention of oxidative stress and degenerative conditions of aging: implications for cognitive health. Oxid Med Cell Longev 2012; 2012: 324832. http://dx.doi.org/10.1155/2012/324832
8. Kang YA, Choi HR, Na JI, et al. Copper-GHK increases integrin expression and p63 positivity by keratinocytes. Arch Dermatol Res 2009; 301: 301-6. http://dx.doi.org/10.1007/s00403-009-0942-x
9. Choi HR, Kang YA, Ryoo SJ, et al. Stem cell recovering effect of copper-free GHK in skin. J Pept Sci 2012; 18: 685-90. http://dx.doi.org/10.1002/psc.2455
10. Campbell JD, McDonough JE, Zeskind JE, et al. A gene expression signature of emphysema-related lung destruction and its reversal by the tripeptide GHK. Genome Med 2012; 4: 67. http://dx.doi.org/10.1186/gm367
11. Hong Y, Downey T, Eu KW, Koh PK, Cheah PY. A " metastasis-prone" signature for early-stage mismatch-repair proficient sporadic colorectal cancer patients and its implications for possible therapeutics. Clin Exp Metastasis 2010; 27: 83-90. http://dx.doi.org/10.1007/s10585-010-9305-4
12. Lamb J, Crawford ED, Peck D, et al. The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease. Science 2006; 313: 1929-35. http://dx.doi.org/10.1126/science.1132939
13. Matalka LE, Ford A, Unlap MT. The tripeptide, GHK, induces programmed cell death in SH-SY5Y neuroblastoma cells. J Biotechnol Biomater 2012; 2: 1-4. http://dx.doi.org/10.4172/2155-952X.1000144
14. Kimoto E, Tanaka H, Gyotoku J, Morishige F, Pauling L. Enhancement of antitumor activity of ascorbate against Ehrlich ascites tumor cells by the copper: glycylglycylhistidine complex. Cancer Res 1983; 43: 824-8.
15. Pickart L, Goodwin WH, Burgua W, Murphy TB, Johnson DK. Inhibition of the growth of cultured cells and an implanted fibrosarcoma by aroylhydrazone analogs of the Gly-His-Lys-Cu(II) complex. Biochem Pharmacol 1983; 32: 3868-71. http://dx.doi.org/10.1016/0006-2952(83)90164-8
16. Simeon A, Wegrowski Y, Bontemps Y, Maquart FX. Expression of glycosaminoglycans and small proteoglycans in wounds: modulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu(2+). J Invest Dermatol 2000; 115: 962-8. http://dx.doi.org/10.1046/j.1523-1747.2000.00166.x
17. Jin T, Curry J, Smith P, Jiang J, Xiao TS. Structure of the NLRP1 caspase recruitment domain suggests potential mechanisms for its association with procaspase-1. Proteins 2013; 81: 1266-70. http://dx.doi.org/10.1002/prot.24287
18. NCBI [internet]. Bethesda, MD: National Center for Biotechnology Information, U.S. National Library of Medicine; [updated 2014 Apr 8; cited 2013 Aug 20]: Available from: http://www.ncbi.nlm.nih.gov/gene/29775
19. NCBI [internet]. Bethesda, MD: National Center for Biotechnology Information, U.S. National Library of Medicine; [updated 2014 Apr 17; cited 2013 Aug 20]: Available from: http://www.ncbi.nlm.nih.gov/gene/79370
20. Liu J, Chung HJ, Vogt M, et al. JTV1 co-activates FBP to induce USP29 transcription and stabilize p53 in response to oxidative stress. EMBO J 2011; 30: 846-58. http://dx.doi.org/10.1038/emboj.2011.11
21. Eriksen KW, Sondergaard H, Woetmann A, et al. The combination of IL-21 and IFN-alpha boosts STAT3 activation, cytotoxicity and experimental tumor therapy. Mol Immunol 2009; 46: 812-20. http://dx.doi.org/10.1016/j.molimm.2008.09.006
22. Zawacka-Pankau J, Kostecka A, Sznarkowska A, Hedstrom E, Kawiak A. p73 tumor suppressor protein: a close relative of p53 not only in structure but also in anti-cancer approach? Cell Cycle 2010; 9: 720-8. http://dx.doi.org/10.4161/cc.9.4.10668
23. Miyata N, Azuma T, Hozawa S, et al. Transforming growth factor beta and Ras/MEK/ERK signaling regulate the expression level of a novel tumor suppressor Lefty. Pancreas 2012; 41: 745-52. http://dx.doi.org/10.1097/MPA.0b013e31823b66d3
24. Furuta S, Jeng YM, Zhou L, et al. IL-25 causes apoptosis of IL-25R-expressing breast cancer cells without toxicity to nonmalignant cells. Sci Transl Med 2011; 3: 78ra31. http://dx.doi.org/10.1126/scitranslmed.300134
25. Ochoa MC, Mazzolini G, Hervas-Stubbs S, de Sanmamed MF, Berraondo P, Melero I. Interleukin-15 in gene therapy of cancer. Curr Gene Ther 2013; 13: 15-30. http://dx.doi.org/10.2174/1566523211313010003
26. Kudoh T, Kimura J, Lu ZG, Miki Y, Yoshida K. D4S234E, a novel p53-responsive gene, induces apoptosis in response to DNA damage. Exp Cell Res 2010; 316: 2849-58. http://dx.doi.org/10.1016/j.yexcr.2010.06.025
27. NCBI [internet]. Bethesda, MD: National Center for Biotechnology Information, U.S. National Library of Medicine; [updated 2014 Apr 8; cited 2013 Aug 20]: Available from: http://www.ncbi.nlm.nih.gov/gene/23281
28. Huisman C, Wisman GB, Kazemier HG, et al. Functional validation of putative tumor suppressor gene C13ORF18 in cervical cancer by Artificial Transcription Factors. Mol Oncol 2013; 7: 669-79. http://dx.doi.org/10.1016/j.molonc.2013.02.017
29. Aguissa-Toure AH, Wong RP, Li G. The ING family tumor suppressors: from structure to function. Cell Mol Life Sci 2011; 68: 45-54. http://dx.doi.org/10.1007/s00018-010-0509-1
30. Vermeulen SJ, Nollet F, Teugels E, et al. The alphaE-catenin gene (CTNNA1) acts as an invasion-suppressor gene in human colon cancer cells. Oncogene 1999; 18: 905-15. http://dx.doi.org/10.1038/sj.onc.1202348
31. Larson PS, Schlechter BL, King CL, et al. CDKN1C/p57kip2 is a candidate tumor suppressor gene in human breast cancer. BMC Cancer 2008; 8: 68. http://dx.doi.org/10.1186/1471-2407-8-68
32. NCBI [internet]. Bethesda, MD: National Center for Biotechnology Information, U.S. National Library of Medicine; [updated 2014 Apr 8; cited 2013 Aug 20]: Available from: http://www.ncbi.nlm.nih.gov/gene/5074
33. Aoki K, Taketo MM. Adenomatous polyposis coli (APC): a multi-functional tumor suppressor gene. J Cell Sci 2007; 120: 3327-35. http://dx.doi.org/10.1242/jcs.03485
34. Chu EC, Tarnawski AS. PTEN regulatory functions in tumor suppression and cell biology. Med Sci Monit 2004; 10: RA235-41.
35. Garcia-Cao I, Song MS, Hobbs RM, et al. Systemic elevation of PTEN induces a tumor-suppressive metabolic state. Cell 2012; 149: 49-62. http://dx.doi.org/10.1016/j.cell.2012.02.030
36. Chua YL, Ito Y, Pole JC, et al. The NRG1 gene is frequently silenced by methylation in breast cancers and is a strong candidate for the 8p tumour suppressor gene. Oncogene 2009; 28: 4041-52. http://dx.doi.org/10.1038/onc.2009.259
37. Dodd RD, Mito JK, Eward WC, et al. NF1 deletion generates multiple subtypes of soft-tissue sarcoma that respond to MEK inhibition. Mol Cancer Ther 2013; 12: 1906-17. http://dx.doi.org/10.1158/1535-7163.MCT-13-0189
38. NCBI [internet]. Bethesda, MD: National Center for Biotechnology Information, U.S. National Library of Medicine; [updated 2014 Apr 21; cited 2013 Aug 20]: Available from: http://www.ncbi.nlm.nih.gov/gene/472
39. Sofeu Feugaing DD, Gotte M, Viola M. More than matrix: the multifaceted role of decorin in cancer. Eur J Cell Biol 2013; 92: 1-11. http://dx.doi.org/10.1016/j.ejcb.2012.08.004
40. Silver DP, Livingston DM. Mechanisms of BRCA1 tumor suppression. Cancer Discov 2012; 2: 679-84. http://dx.doi.org/10.1158/2159-8290.CD-12-0221
41. Krech T, Scheuerer E, Geffers R, Kreipe H, Lehmann U, Christgen M. ABCB1/MDR1 contributes to the anticancer drug-resistant phenotype of IPH-926 human lobular breast cancer cells. Cancer Lett 2012; 315: 153-60. http://dx.doi.org/10.1016/j.canlet.2011.09.038
42. Gu L, Vogiatzi P, Puhr M, et al. Stat5 promotes metastatic behavior of human prostate cancer cells in vitro and in vivo. Endocr Relat Cancer 2010; 17: 481-93. http://dx.doi.org/10.1677/ERC-09-0328
43. Liao RG, Jung J, Tchaicha J, et al. Inhibitor-Sensitive FGFR2 and FGFR3 Mutations in Lung Squamous Cell Carcinoma. Cancer Res 2013; 73: 5195-205. http://dx.doi.org/10.1158/0008-5472.CAN-12-3950
44. Besirli CG, Zheng QD, Reed DM, Zacks DN. ERK-mediated activation of Fas apoptotic inhibitory molecule 2 (Faim2) prevents apoptosis of 661W cells in a model of detachmentinduced photoreceptor cell death. PLoS One 2012; 7: e46664. http://dx.doi.org/10.1371/journal.pone.0046664
45. Key TJ, Appleby PN, Reeves GK, Roddam AW. Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk: pooled individual data analysis of 17 prospective studies. Lancet Oncol 2010; 11: 530-42. http://dx.doi.org/10.1016/S1470-2045(10)70095-4
46. Mocellin S, Nitti D. TNF and cancer: the two sides of the coin. Front Biosci 2008; 13: 2774-83.
47. Pollard JD, Quan S, Kang T, Koch RJ. Effects of copper tripeptide on the growth and expression of growth factors by normal and irradiated fibroblasts. Arch Facial Plast Surg 2005; 7: 27-31. http://dx.doi.org/10.1001/archfaci.7.1.27
48. Iorio F, Bosotti R, Scacheri E, et al. Discovery of drug mode of action and drug repositioning from transcriptional responses. Proc Natl Acad Sci USA 2010; 107: 14621-6. http://dx.doi.org/10.1073/pnas.1000138107
49. Lombard DB, Chua KF, Mostoslavsky R, Franco S, Gostissa M, Alt FW. DNA repair, genome stability, and aging. Cell 2005; 120: 497-512. http://dx.doi.org/10.1016/j.cell.2005.01.028
50. Wolters S, Schumacher B. Genome maintenance and transcription integrity in aging and disease. Front Genet 2013; 4: 19. http://dx.doi.org/10.3389/fgene.2013.00019
51. Diderich K, Alanazi M, Hoeijmakers JH. Premature aging and cancer in nucleotide excision repair-disorders. DNA Repair Amst 2011; 10: 772-80. http://dx.doi.org/10.1016/j.dnarep.2011.04.025
52. Smakhtin MY, Konoplya AI, Severyanova LA, Kurtseva AA, Cherdakov VY. Reparative activity of different functional group peptides in hepatopathyes. Exp Biol Med 2006; 3: 11-7.
53. Cherdakov VY, Smakhtin MY, Dubrovin GM, Dudka VT, Bobyntsev II. Synergetic antioxidant and reparative action of thymogen, dalargin and peptide Gly-His-Lys in tubular bone fractures. Exp Biol Med 2010; 4: 15-20.
54. Hostynek JJ, Dreher F, Maibach HI. Human skin penetration of a copper tripeptide in vitro as a function of skin layer. Inflamm Res 2011; 60: 79-86. http://dx.doi.org/10.1007/s00011-010-0238-9
55. Li P, Nielsen HM, Mullertz A. Oral delivery of peptides and proteins using lipid-based drug delivery systems. Expert Opin Drug Deliv 2012; 9: 1289-304. http://dx.doi.org/10.1517/17425247.2012.717068
56. Swaminathan J, Ehrhardt C. Liposomal delivery of proteins and peptides. Expert Opin Drug Deliv 2012; 9: 1489-503. http://dx.doi.org/10.1517/17425247.2012.735658