title: Bakuchiol suppresses proliferation of skin cancer cells by directly targeting Hck, Blk, and p38 MAP kinase.
abstract: Bakuchiol is a meroterpene present in the medicinal plant Psoralea corylifolia, which has been traditionally used in China, India, Japan and Korea for the treatment of premature ejaculation, knee pain, alopecia spermatorrhea, enuresis, backache, pollakiuria, vitiligo, callus, and psoriasis. Here, we report the chemopreventive properties of bakuchiol, which acts by inhibiting epidermal growth factor (EGF)-induced neoplastic cell transformation. Bakuchiol also decreased viability and inhibited anchorage-independent growth of A431 human epithelial carcinoma cells. Bakuchiol reduced A431 xenograft tumor growth in an in vivo mouse model. Using kinase profiling, we identified Hck, Blk and p38 mitogen activated protein kinase (MAPK) as targets of bakuchiol, which directly bound to each kinase in an ATP-competitive manner. Bakuchiol also inhibited EGF-induced signaling pathways downstream of Hck, Blk and p38 MAPK, including the MEK/ERKs, p38 MAPK/MSK1 and AKT/p70S6K pathways. This report is the first mechanistic study identifying molecular targets for the anticancer activity of bakuchiol and our findings indicate that bakuchiol exhibits potent anticancer activity by targeting Hck, Blk and p38 MAPK.
authors.affiliation: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-742, Republic of Korea.|The Hormel Institute, University of Minnesota, MN 55912, USA.|Advanced Institutes of Convergence Technology, Seoul National University, Suwon 443-270, Republic of Korea.
authors.forename: Jong-Eun
authors.initials: JE
authors.lastname: Kim
authors.affiliation: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Jae Hwan
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Younghyun
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Hee
authors.initials: H
authors.lastname: Yang
authors.affiliation: Advanced Institutes of Convergence Technology, Seoul National University, Suwon 443-270, Republic of Korea.
authors.forename: Yong-Seok
authors.initials: YS
authors.lastname: Heo
authors.affiliation: The Hormel Institute, University of Minnesota, MN 55912, USA.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Bode
authors.affiliation: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-742, Republic of Korea.|Advanced Institutes of Convergence Technology, Seoul National University, Suwon 443-270, Republic of Korea.
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Lee
authors.affiliation: The Hormel Institute, University of Minnesota, MN 55912, USA.
authors.forename: Zigang
authors.initials: Z
authors.lastname: Dong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010636:Phenols / Q000494:pharmacology*; D051572:Proto-Oncogene Proteins c-hck / Q000378:metabolism*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D010636:Phenols; C584409:BLK protein, human; D051572:Proto-Oncogene Proteins c-hck; D019061:src-Family Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C012765:bakuchiol
keywords: Blk; Hck; bakuchiol; cell transformation; p38 MAPK