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2′‐Epi‐2′‐ O ‐acetylthevetin B induces apoptosis partly via Ca 2+ ‐mediated mitochondrial pathway in human hepatocellular carcinoma HepG2 cells
Author(s) -
Feng Bo,
Huang CaiGuo,
Chen RuoHua,
Guo YueWei,
Jiao BingHua
Publication year - 2009
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1016/j.cellbi.2009.06.013
Subject(s) - apoptosis , viability assay , cytosol , egta , annexin , bapta , intracellular , mitochondrion , extracellular , membrane potential , microbiology and biotechnology , programmed cell death , mitochondrial apoptosis induced channel , biology , chemistry , biochemistry , calcium , enzyme , organic chemistry
2′‐Epi‐2′‐ O ‐acetylthevetin B (GHSC‐74), a cardiac glycoside, can be isolated from the seeds of Cerbera manghas L. We demonstrated that GHSC‐74 reduced the viability of HepG2 cells in a time‐ and dose‐dependent manner, and efficiently induced apoptosis without significantly decreasing the viability of Chang human liver cells and Swiss albino 3T3 fibroblasts, as indicated by annexin‐V/PI binding assay and Hoechst 33342 staining. In addition, stimulation of HepG2 cells with GHSC‐74 induced a series of intracellular events: (1) loss of mitochondrial membrane potential; (2) sustained elevation of cytosolic [Ca 2+ ]; and (3) downregulation of Bcl‐2. BAPTA‐AM, a cytosolic Ca 2+ chelator, partly suppressed cell death and prevented mitochondrial membrane potential from losing in GHSC‐74‐treated HepG2 cells. In contrast, EGTA, an extracellular Ca 2+ chelator, exhibited a weaker effect as compared to that of BAPTA‐AM. Taken together, the Ca 2+ ‐mediated mitochondrial pathway was found to be involved in GHSC‐74‐induced HepG2 cell apoptosis.