Yun Xia, Jing Chen, Chongwen Gong, Hongxiang Chen, Jiaming Sun
Department of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (mainland)
Med Sci Monit 2016; 22:1360-1367
The identification and use of novel compounds alone or in combination hold promise for the fight against NRAS mutant melanoma.
MATERIAL AND METHODS: We screened a kinase-specific inhibitor library through combining it with α-Mangostin in NRAS mutant melanoma cell line, and verified the enhancing effect of α-Mangostin through inhibition of the tumorigenesis pathway.
RESULTS: Within the kinase inhibitors, retinoic acid showed a significant synergistic effect with α-Mangostin. α-Mangostin also can reverse the drug resistance of retinoic acid in RARa siRNA-transduced sk-mel-2 cells. Colony assay, TUNEL staining, and the expressions of several apoptosis-related genes revealed that a-Mangostin enhanced the effect of retinoic acid-induced apoptosis. The combination treatment resulted in marked induction of ROS generation and inhibition of the AKT/S6 pathway.
CONCLUSIONS: These results indicate that the combination of these novel natural agents with retinoid acid may be clinically effective in NRAS mutant melanoma.
Keywords: Apoptosis - drug effects, Biological Products - therapeutic use, Cell Line, Tumor, Down-Regulation - drug effects, GTP Phosphohydrolases - genetics, Gene Expression Regulation, Neoplastic - drug effects, Humans, Melanoma - pathology, Membrane Proteins - genetics, Mutation - genetics, Phosphorylation - drug effects, Protein Kinase Inhibitors - pharmacology, Proto-Oncogene Proteins c-akt - metabolism, Reactive Oxygen Species - metabolism, Reproducibility of Results, Signal Transduction - drug effects, Tretinoin - therapeutic use, Xanthones - therapeutic use