title: Several selective protein kinase C inhibitors including procyanidins promote hair growth.
abstract: We have previously reported that procyanidin oligomers selectively promote growth of murine hair epithelial cells in vitro and stimulate anagen induction in vivo. We report here the possible relationship between the protein kinase C-inhibiting activity of procyanidins and their hair-growing activity. Of the procyanidins, procyanidin B-2 and procyanidin C-1, which selectively inhibit protein kinase C, intensively promote hair epithelial cell proliferation in vitro and stimulate anagen induction in vivo. On the other hand, procyanidins, which inhibit both protein kinase C and A, showed relatively low activity in in vitro and in vivo evaluations. We also found that calphostin C, which is a selective inhibitor of protein kinase C, possesses hair epithelial cell growth-promoting activity in vitro and anagen phase-inducing hair-growing activity in vivo. Other selective protein kinase C inhibitors, such as hexadecylphosphocholine, palmitoyl-DL-carnitine chloride, and polymyxin B sulfate, also show marked anagen phase-inducing hair-growing activity in vivo. Nonselective protein kinase inhibitors, such as staurosporine and K252a, inhibit the growth of hair epithelial cells. 1,2-Dioctanoyl-sn-glycerol, a protein kinase C activator, dose-dependently decreases the growth of hair epithelial cells. Forskolin, an adenylate cyclase activator, promotes hair epithelial cell growth and boosts the growth-promoting effect of procyanidin B-2. It is speculated that the hair-growing activity of procyanidins is related to their protein kinase C-inhibiting activity.
authors.affiliation: Tsukuba Research Laboratories, Kyowa Hakko Kogyo Co., Tsukuba, Ibaraki, Japan. tomoya.takahashi@kyowa.co.jp
authors.forename: T
authors.initials: T
authors.lastname: Takahashi
authors.forename: A
authors.initials: A
authors.lastname: Kamimura
authors.forename: A
authors.initials: A
authors.lastname: Shirai
authors.forename: Y
authors.initials: Y
authors.lastname: Yokoo
mesh_terms: D000287:Administration, Topical; D000818:Animals; D044946:Biflavonoids; D002227:Carbazoles / Q000494:pharmacology; D002392:Catechin / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003124:Colorimetry; D004396:Coloring Agents; D004075:Diglycerides / Q000494:pharmacology; D020536:Enzyme Activators / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects; D006197:Hair / Q000187:drug effects* / Q000254:growth & development*; D026121:Indole Alkaloids; D051379:Mice; D009281:Naphthalenes / Q000494:pharmacology; D044945:Proanthocyanidins; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D019311:Staurosporine / Q000494:pharmacology; D013268:Stimulation, Chemical; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D044946:Biflavonoids; D002227:Carbazoles; D004396:Coloring Agents; D004075:Diglycerides; D020536:Enzyme Activators; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; D009281:Naphthalenes; D044945:Proanthocyanidins; D013778:Tetrazolium Salts; D013844:Thiazoles; C044295:1,2-dioctanoylglycerol; C479578:procyanidin B; C479583:procyanidin C; C017674:procyanidin; D002392:Catechin; C049985:staurosporine aglycone; D011493:Protein Kinase C; C022616:thiazolyl blue; D019311:Staurosporine; C058819:calphostin C