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 language | English (US) |
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Pages (from-to) | 107076-107088 |
Number of pages | 13 |
Journal | Oncotarget |
Volume | 8 |
Issue number | 63 |
DOIs | |
State | Published - 2017 |
Externally published | Yes |
Keywords
- AURKA
- Alisertib
- MAPK
- Melanoma
ASJC Scopus subject areas
- Oncology