Roles of SIRT1 and phosphoinositide 3-OH kinase/protein kinase C pathways in evodiamine-induced human melanoma A375-S2 cell death.
We previously demonstrated that evodimine isolated from Evodia rutaecarpa (Goshuyu in Japan) induced apoptosis in human malignant melanoma A375-S2 cells within 24 h. In this study, TUNEL assay also indicated that one cause of A375-S2 cell death induced by evodiamine was apoptosis. After treatment with evodiamine for the indicated time periods, anti-apoptotic protein SIRT1 expression was decreased; p53 expression and its phosphorylation were both enhanced, whereas transient induction of downstream p21 was not enough to promote cell cycle arrest. Inhibition of the phosphoinositide 3-OH kinase (PI3-K)/protein kinase C (PKC) survival pathway as well as subsequent inhibition of the ERK cascade might contribute to evodiamine-induced cell death. In addition, p53 activation in response to evodiamine administration was correlated with the activation of the PI3-K/PKC pro-apoptotic pathway, but did not require ERK participation. The inhibition of the PI3-K/PKC survival pathway might be responsible for SIRT1 inactivation and increased Bax/Bcl-2 expression ratio in evodiamine-induced cell death.
Wang
Che
C
China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, China.
Wang
Min-Wei
MW
Tashiro
Shin-ichi
S
Onodera
Satoshi
S
Ikejima
Takashi
T
D000730:Androstadienes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D032086:Evodia; D015870:Gene Expression / Q000187:drug effects; D016158:Genes, p53 / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1; D037761:Sirtuins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019311:Staurosporine / Q000494:pharmacology; D000077191:Wortmannin; D051028:bcl-2-Associated X Protein
D000730:Androstadienes; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010936:Plant Extracts; D011493:Protein Kinase C; D019253:Proto-Oncogene Proteins c-bcl-2; D011799:Quinazolines; D056564:Sirtuin 1; D037761:Sirtuins; D019311:Staurosporine; D000077191:Wortmannin; D051028:bcl-2-Associated X Protein; C494826:BAX protein, human; C049639:evodiamine; C447939:SIRT1 protein, human