Studies on the Biochemical Mechanisms of anti-tumor effects of Geraniin

• Main Authors: Chiang Min Liang, 梁家銘
• Other Authors: Jen Ken Lin
• Format: Others
• Language: zh-TW
• Published: 2003
• Online Access: http://ndltd.ncl.edu.tw/handle/48709244776494270701

碩士 === 國立臺灣大學 === 生物化學暨分子生物學研究所 === 91 === Geraniin is isolated from geranium.The aim of this study was to investigate the mechanism of geraniin —induced apoptosis in human melanoma cells.In this study, we demonstrated that geraniin was able to induce apoptosis in a concentration- and time-dependent manner.We further investigated the molecular mechanisms of geraniin -induced apoptosis. Immunoblot experiments demonstrated that geraniin induced apoptosis was associated with the up-regulation of Fas ligand expression,the activation of caspase-8 ,caspase-9 and cleavage Bid,and by the induced cytochrome c release from mitochrondia to cytosol.Treatment of geraniin caused induction Caspase 3 /CPP32 activity in a concentration- and time-dependent manner and caused proteolytic cleavage of poly-(ADP-ribose) polymerase(PARP) ,and DNA fragmentation factor 45(DFF45).The recent studies which report the following:(1)FAK suppresses apoptosis in epithelial cells; (2) inhibition of FAK in fibroblasts results in apoptosis;(3) attenuation of FAK induces apoptosis in tumor cells.Furthermore,treatment with geraniin induced FAK degradation in a concentration-and time-dependent manner. Pretreatment with z-Val-Ala-Asp-fluoromethyl-ketone (z-VAD-FMK) caspase-3 inhibitor significantly inhibited geraniin induced FAK cleavaged . These findings are consistent with our evidences that FAK cleavaged processing is in part mediated by caspase 3, and induces apoptosis in human melonoma cells.This induction of apoptosis by geraniin may provide a pivotal mechanism for its cancer chemopreventive action.