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

Yuan-Yuan Shang; Ming Yao; Zhi-Wei Zhou; Jian-Cui; Li-Xia; Rong-Ying Hu; Ying-Yao Yu; Qiong-Gao; Biao-Yang; Yu-Xi Liu; Jie Dang; Shu-Feng Zhou; Nan-Yu

doi:10.18632/oncotarget.22328

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

Oncotarget. 2017 Nov 6;8(63):107076-107088. doi: 10.18632/oncotarget.22328. eCollection 2017 Dec 5.

Authors

Yuan-Yuan Shang^{1

2}, Ming Yao^{3

2}, Zhi-Wei Zhou², Jian-Cui⁴, Li-Xia¹, Rong-Ying Hu¹, Ying-Yao Yu¹, Qiong-Gao¹, Biao-Yang¹, Yu-Xi Liu¹, Jie Dang⁵, Shu-Feng Zhou², Nan-Yu¹

Affiliations

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.

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.

Keywords: AURKA; MAPK; alisertib; melanoma.