Skip to main content

Advertisement

Log in

PAL-12, a new anti-aging hexa-peptoid, inhibits UVB-induced photoaging in human dermal fibroblasts and 3D reconstructed human full skin model, Keraskin-FT™

  • Original Paper
  • Published:
Archives of Dermatological Research Aims and scope Submit manuscript

Abstract

Peptoids are a class of peptidomimetics whose pharmacological activities are widely investigated owing to their remarkable biological stability. However, the utilities of peptoids as cosmetic functional ingredients have not been fully explored. Here, we investigated anti-aging effects of PAL-12, a new hexa-peptoid, on UVB-induced photoaging in human dermal fibroblasts (HDFs) and a 3D reconstituted human full skin model, Keraskin-FT™. PAL-12 suppressed matrix metalloproteinase-1 (MMP-1) expression induced by UVB irradiation along with the attenuation of MMP-1 secretion as determined by ELISA assay. Interestingly PAL-12 slightly enhanced the expression levels of collagen-1 and fibronectin-1 in HDFs or Keraskin-FT™. In addition, PAL-12 prevented the decrease of cell viability following UVB irradiation. However, PAL-12 failed to affect ROS generation, cell necrosis and apoptosis significantly. Instead, PAL-12 suppressed UVB-induced activation of epidermal growth factor receptors (EGFR), extracellular signal-regulated kinase (ERK) and c-Jun, which may resulted in the attenuation of AP-1-promoted MMP-1 expression. Collectively, these results suggest that PAL-12 might be a novel cosmetic ingredient effective against UVB-induced skin photoaging.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. AaronáLau KH (2014) Peptoids for biomaterials science. Biomater Sci 2(5):627–633

    Article  Google Scholar 

  2. Afaq F, Zaid MA, Khan N, Dreher M, Mukhtar H (2009) Protective effect of pomegranate-derived products on UVB-mediated damage in human reconstituted skin. Exp Dermatol 18(6):553–561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Bowden GT (2004) Prevention of non-melanoma skin cancer by targeting ultraviolet-B-light signalling. Nat Rev Cancer 4(1):23–35

    Article  CAS  PubMed  Google Scholar 

  4. Chiu T-M, Huang C-C, Lin T-J, Fang J-Y, Wu N-L, Hung C-F (2009) In vitro and in vivo anti-photoaging effects of an isoflavone extract from soybean cake. J Ethnopharmacol 126(1):108–113

    Article  CAS  PubMed  Google Scholar 

  5. Chung K-Y, Agarwal A, Uitto J, Mauviel A (1996) An AP-1 binding sequence is essential for regulation of the human 2 (I) collagen (COL1A2) promoter activity by transforming growth factor. J Biol Chem 271(6):3272–3278

    Article  CAS  PubMed  Google Scholar 

  6. Davis RJ (1993) The mitogen-activated protein kinase signal transduction pathway. J Biol Chem 268:14553

    CAS  PubMed  Google Scholar 

  7. Di Girolamo N, Wakefield D, Coroneo MT (2006) UVB-mediated induction of cytokines and growth factors in pterygium epithelial cells involves cell surface receptors and intracellular signaling. Invest Ophthalmol Vis Sci 47(6):2430–2437

    Article  PubMed  Google Scholar 

  8. Dohm MT, Kapoor R, Barron AE (2011) Peptoids: bio-inspired polymers as potential pharmaceuticals. Curr Pharm Des 17(25):2732–2747

    Article  CAS  PubMed  Google Scholar 

  9. Duval C, Schmidt R, Regnier M, Facy V, Asselineau D, Bernerd F (2003) The use of reconstructed human skin to evaluate UV-induced modifications and sunscreen efficacy. Exp Dermatol 12(s2):64–70

    Article  CAS  PubMed  Google Scholar 

  10. El-Domyati M, Attia S, Saleh F, Brown D, Birk D, Gasparro F, Ahmad H, Uitto J (2002) Intrinsic aging vs. photoaging: a comparative histopathological, immunohistochemical, and ultrastructural study of skin. Exp Dermatol 11(5):398–405

    Article  CAS  PubMed  Google Scholar 

  11. Fernando PM, Piao MJ, Kang KA, Ryu YS, Hewage SR, Chae SW, Hyun JW (2016) Rosmarinic acid attenuates cell damage against UVB radiation-induced oxidative stress via enhancing antioxidant effects in human HaCaT cells. Biomol Ther (Seoul) 24(1):75–84. doi:10.4062/biomolther.2015.069

    Article  CAS  Google Scholar 

  12. Fisher GJ, Kang S, Varani J, Bata-Csorgo Z, Wan Y, Datta S, Voorhees JJ (2002) Mechanisms of photoaging and chronological skin aging. Arch Dermatol 138(11):1462–1470

    Article  CAS  PubMed  Google Scholar 

  13. Gentilucci L, De Marco R, Cerisoli L (2010) Chemical modifications designed to improve peptide stability: incorporation of non-natural amino acids, pseudo-peptide bonds, and cyclization. Curr Pharm Des 16(28):3185–3203

    Article  CAS  PubMed  Google Scholar 

  14. Gobbo M, Benincasa M, Bertoloni G, Biondi B, Dosselli R, Papini E, Reddi E, Rocchi R, Tavano R, Gennaro R (2009) Substitution of the arginine/leucine residues in apidaecin Ib with peptoid residues: effect on antimicrobial activity, cellular uptake, and proteolytic degradation. J Med Chem 52(16):5197–5206

    Article  CAS  PubMed  Google Scholar 

  15. Hong SI, Kwon SH, Hwang JY, Ma SX, Seo JY, Ko YH, Kim HC, Lee SY, Jang CG (2016) Quinpirole increases melatonin-augmented pentobarbital sleep via cortical ERK, p38 MAPK, and PKC in mice. Biomol Ther (Seoul) 24(2):115–122. doi:10.4062/biomolther.2015.097

    Article  CAS  Google Scholar 

  16. Jang WH, Jung KM, Yang HR, Lee M, Jung HS, Lee SH, Park M, Lim KM (2015) Evaluation of eye irritation potential of solid substance with new 3D reconstructed human cornea model, MCTT HCE(TM). Biomol Ther (Seoul) 23(4):379–385. doi:10.4062/biomolther.2015.004

    Article  CAS  Google Scholar 

  17. Kapoor R, Wadman MW, Dohm MT, Czyzewski AM, Spormann AM, Barron AE (2011) Antimicrobial peptoids are effective against Pseudomonas aeruginosa biofilms. Antimicrob Agents Chemother 55(6):3054–3057

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kato S, Matsui H, Saitoh Y, Miwa N (2011) Fish collagen-containing drink is subcutaneously absorbed and attenuates the UVA-induced tissue-integrity destruction and DNA damages in 3D-human skin tissue model. J Funct Foods 3(1):50–55

    Article  CAS  Google Scholar 

  19. Kessler H (1993) Peptoids—a new approach to the development of pharmaceuticals. Angew Chem, Int Ed Engl 32(4):543–544

    Article  Google Scholar 

  20. Kwon Y-U, Kodadek T (2007) Quantitative evaluation of the relative cell permeability of peptoids and peptides. J Am Chem Soc 129(6):1508–1509

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Lee M, Hwang JH, Lim KM (2017) Alternatives to in vivo draize rabbit eye and skin irritation tests with a focus on 3D reconstructed human cornea-like epithelium and epidermis models. Toxicol Res 33(3):191–203. doi:10.5487/TR.2017.33.3.191

    Article  PubMed  PubMed Central  Google Scholar 

  22. Lee M, Park H, Jeon SW, Bang J, Chung KY, Choi DW, Kim E, Lim K-M (2015) Novel anti-melanogenic hexapeptoids, PAL-10 and PAL-12. Arch Dermatol Res 307(3):249–257

    Article  CAS  PubMed  Google Scholar 

  23. Meyer-Hoffert U, Schroder JM (2011) Epidermal proteases in the pathogenesis of rosacea. J Investig Dermatol Symp Proc 15(1):16–23. doi:10.1038/jidsymp.2011.2

    Article  CAS  PubMed  Google Scholar 

  24. Orrenius S, Gogvadze V, Zhivotovsky B (2007) Mitochondrial oxidative stress: implications for cell death. Annu Rev Pharmacol Toxicol 47:143–183

    Article  CAS  PubMed  Google Scholar 

  25. Ott M, Gogvadze V, Orrenius S, Zhivotovsky B (2007) Mitochondria, oxidative stress and cell death. Apoptosis 12(5):913–922

    Article  CAS  PubMed  Google Scholar 

  26. Pallela R, Na-Young Y, Kim S-K (2010) Anti-photoaging and photoprotective compounds derived from marine organisms. Mar Drugs 8(4):1189–1202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Park M, Han J, Lee CS, Soo BH, Lim KM, Ha H (2013) Carnosic acid, a phenolic diterpene from rosemary, prevents UV-induced expression of matrix metalloproteinases in human skin fibroblasts and keratinocytes. Exp Dermatol 22(5):336–341. doi:10.1111/exd.12138

    Article  CAS  PubMed  Google Scholar 

  28. Quan T, Qin Z, Xia W, Shao Y, Voorhees JJ, Fisher GJ (2009) Matrix-degrading metalloproteinases in photoaging. J Investig Dermatol Symp Proc 14(1):20–24. doi:10.1038/jidsymp.2009.8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Roy O, Caumes C, Esvan Y, Didierjean C, Faure S, Taillefumier C (2013) The tert-butyl side chain: a powerful means to lock peptoid amide bonds in the cis conformation. Org Lett 15(9):2246–2249. doi:10.1021/ol400820y

    Article  CAS  PubMed  Google Scholar 

  30. Saitoh Y, Miyanishi A, Mizuno H, Kato S, Aoshima H, Kokubo K, Miwa N (2011) Super-highly hydroxylated fullerene derivative protects human keratinocytes from UV-induced cell injuries together with the decreases in intracellular ROS generation and DNA damages. J Photochem Photobiol, B 102(1):69–76

    Article  CAS  Google Scholar 

  31. Sakon S, Xue X, Takekawa M, Sasazuki T, Okazaki T, Kojima Y, Piao JH, Yagita H, Okumura K, Doi T (2003) NF-κB inhibits TNF-induced accumulation of ROS that mediate prolonged MAPK activation and necrotic cell death. EMBO J 22(15):3898–3909

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Senior RM, Griffin GL, Mecham RP, Wrenn DS, Prasad KU, Urry DW (1984) Val-Gly-Val-Ala-Pro-Gly, a repeating peptide in elastin, is chemotactic for fibroblasts and monocytes. J Cell Biol 99(3):870–874

    Article  CAS  PubMed  Google Scholar 

  33. Seo JY, Lee SH, Youn CS, Choi HR, G-e Rhie, Cho KH, Kim KH, Park KC, Eun HC, Chung JH (2001) Ultraviolet radiation increases tropoelastin mRNA expression in the epidermis of human skin in vivo. J Invest Dermatol 116(6):915–919

    Article  CAS  PubMed  Google Scholar 

  34. Singh B, Schneider M, Knyazev P, Ullrich A (2009) UV-induced EGFR signal transactivation is dependent on proligand shedding by activated metalloproteases in skin cancer cell lines. Int J Cancer 124(3):531–539

    Article  CAS  PubMed  Google Scholar 

  35. Sun J, Zuckermann RN (2013) Peptoid polymers: a highly designable bioinspired material. ACS Nano 7(6):4715–4732. doi:10.1021/nn4015714

    Article  CAS  PubMed  Google Scholar 

  36. Uitto J, Bernstein EF (1998) Molecular mechanisms of cutaneous aging: connective tissue alterations in the dermis. J Investig Dermatol Symp Proc 3(1):41–44

    CAS  PubMed  Google Scholar 

  37. Warren R, Gartstein V, Kligman AM, Montagna W, Allendorf RA, Ridder GM (1991) Age, sunlight, and facial skin: a histologic and quantitative study. J Am Acad Dermatol 25(5 Pt 1):751–760

    Article  CAS  PubMed  Google Scholar 

  38. Watson RE, Gibbs NK, Griffiths CE, Sherratt MJ (2014) Damage to skin extracellular matrix induced by UV exposure. Antioxid Redox Signal 21(7):1063–1077

    Article  CAS  PubMed  Google Scholar 

  39. Whitmarsh A, Davis R (1996) Transcription factor AP-1 regulation by mitogen-activated protein kinase signal transduction pathways. J Mol Med 74(10):589–607

    Article  CAS  PubMed  Google Scholar 

  40. Wlaschek M, Tantcheva-Poór I, Naderi L, Ma W, Schneider LA, Razi-Wolf Z, Schüller J, Scharffetter-Kochanek K (2001) Solar UV irradiation and dermal photoaging. J Photochem Photobiol B 63(1):41–51

    Article  CAS  PubMed  Google Scholar 

  41. Xu Y, Fisher GJ (2005) Ultraviolet (UV) light irradiation induced signal transduction in skin photoaging. J Dermatol Sci Suppl 1(2):S1–S8

    CAS  Google Scholar 

  42. Zhang H, Cui R, Guo X, Hu J, Dai J (2016) Low dose perfluorooctanoate exposure promotes cell proliferation in a human non-tumor liver cell line. J Hazard Mater 313:18–28

    Article  CAS  PubMed  Google Scholar 

  43. Zhang L, Falla TJ (2009) Cosmeceuticals and peptides. Clin Dermatol 27(5):485–494

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by grants of the Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (Grant no. HN13C0077) and the Small and Medium Business Administration Project, Republic of Korea (C0483208).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Eun-Joo Kim or Kyung-Min Lim.

Ethics declarations

Conflict of interest

The authors declare that there are no conflicts of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Song, D., Park, H., Lee, SH. et al. PAL-12, a new anti-aging hexa-peptoid, inhibits UVB-induced photoaging in human dermal fibroblasts and 3D reconstructed human full skin model, Keraskin-FT™. Arch Dermatol Res 309, 697–707 (2017). https://doi.org/10.1007/s00403-017-1768-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00403-017-1768-6

Keywords

Navigation