Oncotarget

Research Papers:

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 _ and Nan Yu

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Oncotarget. 2017; 8:107076-107088. https://doi.org/10.18632/oncotarget.22328

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Abstract

Yuan-Yuan Shang1,2,*, Ming Yao3,2,*, 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 and Nan-Yu1

1Department of Dermatology, General Hospital of NingXia Medical University, Yinchuan, P.R. China

2Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA

3Department of Burns and Plastic Surgery, General Hospital of NingXia Medical University, Yinchuan, P.R. China

4Department of Anesthesia, General Hospital of NingXia Medical University, Yinchuan, P.R. China

5Department 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: [email protected]

Nan-Yu, email: [email protected]

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.


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