Alisertib promotes apoptosis and autophagy in melanoma through p38 MAPK-mediated aurora a signaling

Abstract

// Yuan-Yuan Shang 1, 2, * , Ming Yao 3, 2, * , Zhi-Wei Zhou 2 , Jian-Cui 4 , Li-Xia 1 , Rong-Ying Hu 1 , Ying-Yao Yu 1 , Qiong-Gao 1 , Biao-Yang 1 , Yu-Xi Liu 1 , Jie Dang 5 , Shu-Feng Zhou 2 and Nan-Yu 1 1 Department of Dermatology, General Hospital of NingXia Medical University, Yinchuan, P.R. China 2 Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA 3 Department of Burns and Plastic Surgery, General Hospital of NingXia Medical University, Yinchuan, P.R. China 4 Department of Anesthesia, General Hospital of NingXia Medical University, Yinchuan, P.R. China 5 Department of Medical Genetics and Cell Biology, Ningxia Medical University, Yinchuan, P.R.China * These authors have contributed equally to this work Correspondence to: Shu-Feng Zhou, email: szhou@health.usf.edu Nan-Yu, email: syy23301@163.com Keywords: alisertib; melanoma; AURKA; MAPK Received: June 06, 2017     Accepted: September 21, 2017     Published: November 06, 2017 ABSTRACT We investigated the efficacy of Alisertib (ALS), a selective Aurora kinase A (AURKA) inhibitor, in melanoma. We found that ALS exerts anti-proliferative, pro-apoptotic, and pro-autophagic effects on A375 and skmel-5 melanoma cells by inhibiting p38 MAPK signaling. SB202190, a p38 MAPK-selective inhibitor, enhanced ALS-induced apoptosis and autophagy in both cell lines. ALS induced cell cycle arrest in melanoma cells through activation of the p53/p21/cyclin B1 pathway. Knockdown of p38 MAPK enhanced ALS-induced apoptosis and reduced ALS-induced autophagy. Inhibition of autophagy sensitized melanoma cells to ALS-induced apoptosis. These data indicate ALS is a potential therapeutic agent for melanoma.