Gypenosides induce apoptosis and metastasis inhibition in human tongue squamous carcinoma cells (SCC4)

• Main Authors: Ming-Li Tsai, 蔡明俐
• Other Authors: 陳榮洲
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/45289126921742092700

碩士 === 中國醫藥大學 === 中國醫學研究所碩士班 === 95 === Gynostemma pentaphyllum (GP) is one of the Chinese medical herbs. Gypenosides (Gyps) is a major compound of Gynostemma pentaphyllum Makino. Clinical researches indicated that gypenosides have various pharmacological effects including anti-tumor effects, decreasing blood lipid, antioxidation effect,enhancing immune capacity effect,promoting live functions etc. Previous studies have shown that gypenosides induced cytotoxicity, G0/ G1 arrest of cell cycle and apoptosis in human colon, breast and liver cancer cell lines underwent the activation of caspase 3. However, the molecular mechanism underlying the gypenosides induced apoptotic process and inhibition of metastasis are still unclear. In the present studies, we have observed that treated SCC4 cells with gypenosides resulted in a dose- and time-dependent decrease in cell viability. Furthermor, we found the gypenoside induced apoptosis in human tongue squamous carcinoma cells (SCC4) by morphological changes, DAPI staining , comet assay and DNA fragmentation agarose gel electrophoresis. In this study,the Western blot will be used for detecting cell cycle associate protein and apoptosis. The data display that Gyps induced G0/ G1 phase arrest of cell cycle in SCC4 cells through the up-regulation of chk2, p53, p21, p16, and down-regulation of cyclin D, cyclin E, cdk6,. These results suggest that Gyps induced apoptosis through (1) the mitochondria-dependent pathways: up-regulation of Bax, cytochrome c, caspase 9, caspase 3, and down-regulation of BcL-2, BcL-XL.(2) the death receptor-dependent pathways: up-regulation of TRAIL、caspase 8、Bid (3) the endoplasmic reticulum-dependent pathways: up-regulation of Ca2+、caspase 12 and down-regulation of GRP78 (4) the redox signaling pathways: up-regulation of ROS, SOD, GST, catalase (5) MAPKs pathways: up-regulation of JNK1/2, p38 and down-regulation of ERK1/2. Our results indicated that Gyps induced inhibition of metastasis in SCC4 cells through the。Ras/ NFκB/ iNOS/ COX-2/ p53 pathway or Ras/ ERK1/2 pathway and decreased the expression of MMP 2 and MMP 9.