alisertib; melanoma; AURKA; MAPK
Digital Object Identifier (DOI)
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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Citation / Publisher Attribution
Oncotarget, v. 8, issue 63, p. 107076-107088
Scholar Commons Citation
Shang, Yuan-Yuan; Yao, Ming; Zhou, Zhi-Wei; Cui, Jian; Xia, Li; Hu, Rong-Ying; Yu, Ying-Yao; Gao, Qiong; Yang, Biao; Liu, Yu-Xi; Dang, Jie; Zhou, Shu-Feng; and Yu, Nan, "Alisertib Promotes Apoptosis and Autophagy in Melanoma Through p38 MAPK-mediated Aurora a Signaling" (2017). Pharmacy Faculty Publications. 85.