Roles of SIRT1 and Phosphoinositide 3-OH Kinase/Protein Kinase C Pathways in Evodiamine-Induced Human Melanoma A375-S2 Cell Death

Journal of Pharmacological Sciences

Satoshi Onodera²  Takashi Ikejima¹  Shin-ichi Tashiro²  Che Wang¹  Min-wei Wang³ 

[1] China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University;Department of Clinical and Biomedical Sciences, Showa Pharmaceutical University;Department of Pharmacology, Shenyang Pharmaceutical University

关键词: evodiamine;    SIRT1;    phosphoinositide 3-OH kinase;    protein kinase C;    p53;   

DOI  :  10.1254/jphs.FPJ04055X

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(37)Cited-By(13)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.

【 授权许可】

Unknown