α-Mangostin, a Natural Agent, Enhances the Response of NRAS Mutant Melanoma to Retinoic Acid.
BACKGROUND 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.
Department of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (mainland).
Yun
Y
Xia
Department of Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (mainland).
Jing
J
Chen
Department of Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (mainland).
Chongwen
C
Gong
Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (mainland).
Hongxiang
H
Chen
Department of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (mainland).
Jiaming
J
Sun
D017209:Apoptosis / Q000187:drug effects; D001688:Biological Products / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D020558:GTP Phosphohydrolases / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology / Q000627:therapeutic use*; D044004:Xanthones / Q000494:pharmacology / Q000627:therapeutic use*
D001688:Biological Products; D008565:Membrane Proteins; D047428:Protein Kinase Inhibitors; D017382:Reactive Oxygen Species; D044004:Xanthones; D014212:Tretinoin; D051057:Proto-Oncogene Proteins c-akt; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; C021053:mangostin