Alisertib Promotes Apoptosis and Autophagy in Melanoma Through P38 MAPK-mediated Aurora a Signaling

Overview

Journal Oncotarget

Specialty Oncology

Date 2018 Jan 2

PMID 29291012

Citations 13

Authors

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

Affiliations

Soon will be listed here.

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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