Alisertib promotes apoptosis and autophagy in melanoma through p38 MAPK-mediated aurora a signaling.
Oncotarget
; 8(63): 107076-107088, 2017 Dec 05.
Article
em En
| MEDLINE
| ID: mdl-29291012
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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MEDLINE
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Ano de publicação:
2017
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Article