Bakuchiol suppresses proliferation of skin cancer cells by directly targeting Hck, Blk, and p38 MAP kinase

// Jong-Eun Kim 1, 2, 3, * , Jae Hwan Kim 1, * , Younghyun Lee 1 , Hee Yang 1 , Yong-Seok Heo 4 , Ann M. Bode 2 , Ki Won Lee 1, 3 , Zigang Dong 2 1 Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-742, Republic of Korea 2 The Hormel Institute, University of Minnesota, MN 55912, USA 3 Advanced Institutes of Convergence Technology, Seoul National University, Suwon 443-270, Republic of Korea 4 Department of Chemistry, Konkuk University, Seoul 143-701, Republic of Korea * These authors have contributed equally to this work Correspondence to: Zigang Dong, e-mail: zgdong@hi.umn.edu Ki Won Lee, e-mail: kiwon@snu.ac.kr Keywords: bakuchiol, cell transformation, Blk, Hck, p38 MAPK Received: September 22, 2015      Accepted: January 29, 2016      Published: February 20, 2016 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/p70 S6K 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.