Effect of minoxidil on proliferation and apoptosis in dermal papilla cells of human hair follicle

Background: Minoxidil has been widely used to treat androgenetic alopecia, but little is known about its pharmacological activity or about the identity of its target cells in hair follicles. We hypothesized that minoxidil has direct effects on the proliferation and apoptosis of dermal papilla cells (DPCs) of human hair follicle. Objective: To elucidate the mechanism of topical minoxidil action in terms of stimulating hair growth. Methods: We evaluated cell proliferations in cultured DPCs by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and measured the expressions of extracellular signal-regulated kinase (ERK), Akt, Bct-2, and Bax by Western blot. We also measured elongation of hair follicles in organ culture. Results: Minoxidil significantly increased the proliferation of DPCs. The levels of ERK phosphorylation and of phosphorylated At increased significantly 1 h post-treatment; percentage increase of ERK phosphorylation was 287% at 0.1 muM and 351% at 1.0 muM of minoxidil, and that of At phosphorylation was 168% at 0.1 muM and 257% at 1.0 muM of minoxidil. 1.0 muM of minoxidil increased Bct-2 expression over 150%, while 1.0 muM of minoxidil decreased Bax expression by more than 50%. Moreover, a significant elongation of individual hair follicles in organ culture was observed after adding minoxidil. Conclusion: Minoxidil promotes the survival of human DPCs by activating both ERK and At and by preventing cell death by increasing the ratio of Bcl-2/Bax. We suggest that minoxidil stimulates the growth of human hairs by prolonging anagen through these proliferative and anti-apoptotic effects on DPCs. (C) 2004 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.