title: MST1 activation by curcumin mediates JNK activation, Foxo3a nuclear translocation and apoptosis in melanoma cells.
abstract: Different groups including ours have shown that curcumin induces melanoma cell apoptosis, here we focused the role of mammalian Sterile 20-like kinase 1 (MST1) in it. We observed that curcumin activated MST1-dependent apoptosis in cultured melanoma cells. MST1 silencing by RNA interference (RNAi) suppressed curcumin-induced cell apoptosis, while MST1 over-expressing increased curcumin sensitivity. Meanwhile, curcumin induced reactive oxygen species (ROS) production in melanoma cells, and the ROS scavenger, N-acetyl-cysteine (NAC), almost blocked MST1 activation to suggest that ROS might be required for MST1 activation by curcumin. c-Jun N-terminal protein kinase (JNK) activation by curcumin was dependent on MST1, since MST1 inhibition by RNAi or NAC largely inhibited curcumin-induced JNK activation. Further, curcumin induced Foxo3 nuclear translocation and Bim-1 (Foxo3 target gene) expression in melanoma cells, such an effect by curcumin was inhibited by MST1 RNAi. In conclusion, we suggested that MST1 activation by curcumin mediates JNK activation, Foxo3a nuclear translocation and apoptosis in melanoma cells.
authors.affiliation: Department of Dermatology, Shandong Ji-ning No. 1 People's Hospital, Shandong Province 272011, PR China. Electronic address: tengyu33@yahoo.com.
authors.forename: Teng
authors.initials: T
authors.lastname: Yu
authors.forename: Jiang
authors.initials: J
authors.lastname: Ji
authors.forename: Yong-li
authors.initials: YL
authors.lastname: Guo
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D003474:Curcumin / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008545:Melanoma / Q000201:enzymology* / Q000473:pathology; D008546:Melanoma, Experimental / Q000201:enzymology / Q000473:pathology; D051379:Mice; D021381:Protein Transport / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse; D011518:Proto-Oncogene Proteins; D017382:Reactive Oxygen Species; C082332:macrophage stimulating protein; D017228:Hepatocyte Growth Factor; D048031:JNK Mitogen-Activated Protein Kinases; D003474:Curcumin; D000111:Acetylcysteine
keywords: 3-(4,5-dimethyl-thiazol-2-yl)2,5-diphenyl tetrazolium bromide; Apoptosis; Curcumin; IP; JNK; JNK and Foxo3a; MST1; MTT; Melanoma; N-acetyl-cysteine; NAC; RNA interference; RNAi; ROS; c-Jun N-terminal protein kinase; immunoprecipitation; mammalian Sterile 20-like kinase 1; reactive oxygen species