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.
Highlights
Melanoma is a malignant cancer that arises from melanocytes
We investigated the effects of ALS, a potent and selective inhibitor of Aurora kinase A (AURKA), on melanoma cells
Apoptosis is the principal mechanism of programmed cell death in mammalian cells, autophagy can have a pro-death or a pro-survival role depending on the strength of specific stimuli and on cell type [20, 21]
Summary
Melanoma is a malignant cancer that arises from melanocytes. 132,000 individuals are diagnosed with melanoma each year. The 5-year survival rate of patients with metastatic melanoma is less than 20% [1]. Chemotherapy, radiation therapy, immunotherapy, and targeted therapy. Targeted therapy is considered the most effective. The discovery of mutations in BRAF in melanoma lead to the development of vemurafenib, an orally available and well-tolerated selective inhibitor of BRAF V600E, for the treatment of patients with advanced disease [2]. There are few other biomarkers that can predict treatment response in melanoma patients and additional treatment strategies are needed [3]
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