Skip to main content
Log in

The effect of tripeptide-copper complex on human hair growth in vitro

  • Article
  • Drug efficacy and safety
  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript


The tripeptide-copper complex, described as a growth factor for various kinds of differentiated cells, stimulates the proliferation of dermal fibroblasts and elevates the production of vascular endothelial growth factor, but decreased the secretion of transforming growth factor-β1 by dermal fibroblasts. Dermal papilla cells (DPCs) are specialized fibroblasts, which are important in the morphogenesis and growth of hair follicles. In the present study, the effects of L-alanyl-L-histidy l-L-lysine-Cu2+ (AHK-Cu) on human hair growthex vivo and cultured dermal papilla cells were evaluated. AHK-Cu (10-12-10-9M) stimulated the elongation of human hair folliclesex vivo and the proliferation of DPCsin vitro. Annexin V-fluorescein isothiocyanate/propidium iodide labeling and flow cytometric analysis showed that 10-9M AHK-Cu reduced the number of apoptotic DPCs, but this decrease was not statistically significant. The ratio of Bcl-2/Bax was elevated, and the levels of the cleaved forms of caspase-3 and PARP were reduced by treatment with 10-9M AHK-Cu. The present study proposed that AHK-Cu promotes the growth of human hair follicles, and this stimulatory effect may occur due to stimulation of the proliferation and the preclusion of the apoptosis of DPCs.

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.

Similar content being viewed by others


  • Han, J. H., Kwon, O. S., Chung, J. H., Cho, K. H., Eun, H. C., and Kim, K. H., Effect of minoxidil on proliferation and apoptosis in dermal papilla cells of human hair follicle.J. Dermatol. Sci., 34, 91–98 (2004).

    Article  PubMed  CAS  Google Scholar 

  • Inui, S., Fukuzato, Y, Nakajima, T., Yoshikawa, K., and Itami, S., Identification of androgen-inducible TGF-beta1 derived from dermal papilla cells as a key mediator in androgenetic alopecia.J. Investig. Dermatol. Symp. Proc, 8,69–71 (2003)

    Article  PubMed  CAS  Google Scholar 

  • Jahoda, C. A., Reynolds, A., and Oliver, R. F., Induction of hair growth in ear wounds by cultured dermal papilla cells.J. Invest. Dermatol., 101, 584–590 (1993).

    Article  PubMed  CAS  Google Scholar 

  • Krugluger, W., Rohrbacher, W., Laciak, K., Moser, K., Moser, C, and Hugenneck J., Reorganization of hair follicles in human skin organ culture induced by cultured human follicle-derived cells.Exp. Dermatol., 14, 580–585 (2005).

    Article  PubMed  Google Scholar 

  • Magerl, M., Paus, R., Farjo, N., Muller-Rover, S., Peters, E. M., Foitzik, K., and Tobin, D. J., Limitations of human occipital scalp hair follicle organ culture for studying the effects of minoxidil as a hair growth enhancer.Exp. Dermatol, 13, 635–642 (2004).

    Article  PubMed  CAS  Google Scholar 

  • Maquart, F. X., Bellon, G., Chaqour, B., Wegrowski, J., Patt, L. M., Trachy, R. E., Monboisse, J. C, Chastang, R, Birembaut, P., and Gillery, P., In vivo stimulation of connective tissue accumulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ in rat experimental wounds.J. Clin. Invest, 92, 2368–2376 (1993).

    Article  PubMed  CAS  Google Scholar 

  • Matsuzaki, T. and Yoshizato, K., Role of hair papilla cells on induction and regeneration processes of hair follicles.Wound Repair Regen., 6, 524–430 (1998).

    Article  PubMed  CAS  Google Scholar 

  • McCormack, M. C, Nowak, K. C, and Koch, R. J., The effect of copper tripeptide and tretinoin on growth factor production in a serum-free fibroblast model.Arch Facial. Plast. Surg., 3, 28–32(2001).

    PubMed  CAS  Google Scholar 

  • Messenger, A. G., The culture of dermal papilla cells from human hair follicles.Br J Dermatol., 110,685–689 (1984).

    Article  PubMed  CAS  Google Scholar 

  • Nicholson, D. W., Ali, A., Thomberry, N. A., Vaillancourt, J. P., Ding, C. K., Gallant, M., Gareau, Y, Griffin, P. R., Labelle, M., Lazebnik, Y A., Munday, N. A., Raju, S. M., Smulson, M. E., Yamin, T., Yu, V. L, and Miller, D. K., Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis.Nature, 376, 37–43 (1995).

    Article  PubMed  CAS  Google Scholar 

  • Nunez, G and Clarke, M. R, The Bcl-2 family of proteins: regulators of cell death and survival.Trends. Cell. Biol., 4, 399–403 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Philpott, M. P., Sanders, D. A., and Kealey, T., Whole hair follicle culture.Dermatol. Clin., 14, 595–607 (1996).

    Article  PubMed  CAS  Google Scholar 

  • Pollard, J. D., Quan, S, Kang, T, and Koch, R. J., Effects of copper tripeptide on the growth and expression of growth factors by normal and irradiated fibroblasts.Arch. Facial. Plast. Surg., 7, 27–31 (2005)

    Article  PubMed  Google Scholar 

  • Rhee, H., Polak, L, and Fuchs, E., Lhx2 maintains stem cell character in hair follicles.Science, 312,1946–1949 (2006).

    Article  PubMed  CAS  Google Scholar 

  • Sawaya, M. E., Blume-Peytavi, U., Mullins, D. L, Nusbaum, B. P., Whiting, D., Nicholson, D. W., Lotocki, G, and Keane, R.W., Effects of finasteride on apoptosis and regulation of the human hair cycle.J. Cutan. Med. Surg., 6,1–9 (2002).

    PubMed  Google Scholar 

  • Soma, T. and Hibino, T, Dominant Bcl-2 expression during telogen-anagen transition phase in human hair.J Dermatol Sci., 36, 183–185(2004)

    Article  PubMed  CAS  Google Scholar 

  • Thibaut, S., Collin, C, Langbein, L., Schweizer, J., Gautier, B., and Bernard, B. A., Hair keratin pattern in human hair follicles grown in vitro.Exp. Dermatol., 12,160–164 (2003).

    Article  PubMed  CAS  Google Scholar 

  • Yano, K., Brown, L. F., and Detmar, M., Control of hair growth and follicle size by VEGF-mediated angiogenesis.J. Clin. Invest, 107, 409–417 (2001)

    Article  PubMed  CAS  Google Scholar 

  • Yu, L. F., Wang, J., Zou, B., Lin, M. C, Wu, Y L, Xia, H. H., Sun, Y W., Gu, Q., He, H., Lam, S. K., Kung, H. F., and Wong, B. C, XAF1 mediates apoptosis through an extracellular signal-regulated kinase pathway in colon cancer.Cancer, 2007 (in press)

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to Kyu Han Kim.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pyo, H.K., Yoo, H.G., Won, C.H. et al. The effect of tripeptide-copper complex on human hair growth in vitro. Arch Pharm Res 30, 834–839 (2007).

Download citation

  • Received:

  • Issue Date:

  • DOI:

Key words