title: Hair Growth Promoting and Anticancer Effects of p21-activated kinase 1 (PAK1) Inhibitors Isolated from Different Parts of Alpinia zerumbet.
abstract: PAK1 (p21-activated kinase 1) is an emerging target for the treatment of hair loss (alopecia) and cancer; therefore, the search for PAK1 blockers to treat these PAK1-dependent disorders has received much attention. In this study, we evaluated the anti-alopecia and anticancer effects of PAK1 inhibitors isolated fromAlpinia zerumbet(alpinia) in cell culture. The bioactive compounds isolated from alpinia were found to markedly promote hair cell growth. Kaempferol-3-O-β-d-glucuronide (KOG) and labdadiene, two of the isolated compounds, increased the proliferation of human follicle dermal papilla cells by approximately 117%-180% and 132%-226%, respectively, at 10-100 μM. MTD (2,5-bis(1E,3E,5E)-6-methoxyhexa-1,3,5-trien-1-yl)-2,5-dihydrofuran) and TMOQ ((E)-2,2,3,3-tetramethyl-8-methylene-7-(oct-6-en-1-yl)octahydro-1H-quinolizine) showed growth-promoting activity around 164% and 139% at 10 μM, respectively. The hair cell proliferation induced by these compounds was significantly higher than that of minoxidil, a commercially available treatment for hair loss. Furthermore, the isolated compounds from alpinia exhibited anticancer activity against A549 lung cancer cells with IC50in the range of 67-99 μM. Regarding the mechanism underlying their action, we hypothesized that the anti-alopecia and anticancer activities of these compounds could be attributed to the inhibition of the oncogenic/aging kinase PAK1.
authors.affiliation: Department of Bioscience and Biotechnology, The United Graduate School of Agricultural Sciences, Kagoshima University, Korimoto 1-21-24, Kagoshima 890-8580, Japan. taira5935@gmail.com.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Taira
authors.affiliation: Department of Bioscience and Biotechnology, The United Graduate School of Agricultural Sciences, Kagoshima University, Korimoto 1-21-24, Kagoshima 890-8580, Japan. ncqbinh@gmail.com.|PAK Research Center, University of the Ryukyus, Okinawa 903-0213, Japan. ncqbinh@gmail.com.
authors.forename: Binh Cao Quan
authors.initials: BC
authors.lastname: Nguyen
authors.affiliation: PAK Research Center, University of the Ryukyus, Okinawa 903-0213, Japan. b986097@agr.u-ryukyu.ac.jp.
authors.forename: Shinkichi
authors.initials: S
authors.lastname: Tawata
mesh_terms: D032429:Alpinia / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D035264:Flowers / Q000737:chemistry; D005663:Furans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D015870:Gene Expression; D020719:Glucuronides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018859:Hair Follicle / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D044949:Kaempferols / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008914:Minoxidil / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D011807:Quinolizines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D027343:Rhizome / Q000737:chemistry; D054462:p21-Activated Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004224:Diterpenes; D005663:Furans; D020719:Glucuronides; D044949:Kaempferols; D047428:Protein Kinase Inhibitors; D011807:Quinolizines; C000615701:kaempferol-3-O-glucuronide; D008914:Minoxidil; C515903:PAK1 protein, human; D054462:p21-Activated Kinases
keywords: ">d-glucuronide; Alpinia zerumbet; PAK1 inhibitors; cancer; hair growth; kaempferol-3-O-β-