Gypenosides induced apoptosis in human colon cancer cells through the mitochondria-dependent pathways and activation of caspase-3.
The effects of the gypenosides (Gyp), a component of Gynostemma pentaphyllum Makino, on the cell viability, cell cycle and induction of apoptosis were investigated in human colon cancer colo 205 cells. Gyp was cytotoxic to colo 205 cells with an IC50 of 113.5 microg/ml. The decreasing number of viable cells appeared to be due to the induction of cell cycle arrest and apoptotic cell death, since Gyp induced morphological changes and internucleosomal DNA fragmentation and increased the sub-G1 group. The production of reactive oxygen species and Ca2+ and the depolarization of mitochondrial membrane potential were observed, dose- and time-dependently, after treatment with various concentrations of Gyp. Gyp treatment also gradually decreased the expression of the anti-apoptotic proteins Bcl-2 and Bcl-xl, but increased the expression of the pro-apoptotic protein Bax. Gyp increased the levels of p53 and promoted the release of cytochrome c and the activation of caspase-3 before leading to apoptosis. These results provide information towards an understanding of the mechanisms by which Gyp induces cell cycle arrest and apoptosis in human colon cancer cells.
Chen
Jung-Chou
JC
Chinese Medical Research Institute, China Medical University, Taichung, Taiwan, ROC.
Lu
Kung-Wen
KW
Lee
Jau-Hong
JH
Yeh
Chin-Chung
CC
Chung
Jing-Gung
JG
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism*; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D029774:Gynostemma; D006801:Humans; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology
D010936:Plant Extracts; C474918:gypenoside; D053148:Caspase 3