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, Bcl-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 Akt increased significantly 1 h post-treatment; percentage increase of ERK phosphorylation was 287% at 0.1 microM and 351% at 1.0 microM of minoxidil, and that of Akt phosphorylation was 168% at 0.1 microM and 257% at 1.0 microM of minoxidil. 1.0 microM of minoxidil increased Bcl-2 expression over 150%, while 1.0 microM 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.


CONCLUSIONS
Minoxidil promotes the survival of human DPCs by activating both ERK and Akt 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.
Han
Ji Hyun
JH
Department of Dermatology, Clinical Research Institute, Seoul National University College of Medicine, Seoul National University Hospital, 28 Yongon-Dong, Chongno-Gu, Seoul 110-744, South Korea.
Kwon
Oh Sang
OS
Chung
Jin Ho
JH
Cho
Kwang Hyun
KH
Eun
Hee Chul
HC
Kim
Kyu Han
KH
D000328:Adult; D000505:Alopecia / Q000188:drug therapy; D017209:Apoptosis / Q000187:drug effects*; D018929:Cell Culture Techniques; D002455:Cell Division / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006133:Growth Substances / Q000378:metabolism; D018859:Hair Follicle / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D008914:Minoxidil / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000378:metabolism; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D006133:Growth Substances; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D008914:Minoxidil; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases