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

Research output: Contribution to journalArticlepeer-review

Abstract

We investigated the efficacy of Alisertib (ALS), a selective Aurora kinase A (AURKA) inhibitor, in melanoma. We found that ALS exerts anti-proliferative, proapoptotic, 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.

Original languageEnglish (US)
Pages (from-to)107076-107088
Number of pages13
JournalOncotarget
Volume8
Issue number63
DOIs
StatePublished - 2017
Externally publishedYes

Keywords

  • AURKA
  • Alisertib
  • MAPK
  • Melanoma

ASJC Scopus subject areas

  • Oncology

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