Difference of Susceptivity in Different Tumor Cells to (-)-Epigallocatechin-3-Gallate-Mediated Cytotoxicity and its Possible Molecular Mechanism

Objective To investigate (-)-epigallocatechin-3-gallate (EGCG)-mediated cytotoxicity to colon carcinoma LoVo cells,gastric carcinoma MGC-803 cells and hepatic carcinoma BEL-7402 cells,difference in the cytotoxicity,and its possible molecular mechanism.Methods In the presence or absence of pretreatment with DL-buthionine-[S,R]-sulfoximine(BSO),a glutathione synthesis enzyme inhibitor,the cytotoxcity of EGCG to LoVo cells,MGC-803 cells and BEL-7402 cells were tested by tetrazolium salt MTT assay and trypan blue exclusion.The changes of GSH content and expression of bcl-2 protein were determined by ultraviolet spectrophotography and flow cytometry after treatment of the cells with BSO.Results EGCG had the cytotoxicity to LoVo cells,MGC-803 cells and BEL-7402 cells,but there was difference in the extent of cytotoxicity,of which LoVo cells was the most susceptive to EGCG,MGC-803 was the next,and BEL-7402 was the least.Their IC50 value was 125.30,188.52 and 264.53 μg/ml,respectively.Pretreatment of the three tumor cells with BSO,resulting in a decrease in intracellular GSH content in time-dependent manner,markedly enhanced the susceptivity of the tumor cells to EGCG,and down-regulated the expression level of bcl-2 protein in MGC-803 cells and BEL-7402 cells with time-dependence.Conclusion The difference in cytotoxicity of EGCG to the three tumor cells is associated with intracellular glutathione content.Interaction with intracellular glutathione and bcl-2 protein is possible molecular mechanism.