Document Type

Article

Publication Date

2017

Keywords

alisertib; melanoma; AURKA; MAPK

Digital Object Identifier (DOI)

https://doi.org/10.18632/oncotarget.22328

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.

Rights Information

Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.

Was this content written or created while at USF?

Yes

Citation / Publisher Attribution

Oncotarget, v. 8, issue 63, p. 107076-107088

Share

COinS