ABSTRACT
The aim of the present study was to investigate the effects of deoxycholic acid (DCA) on BGC823 human gastric carcinoma cells and to explore the possible mechanisms underlying any such effects. Cell proliferation was detected using a 3(4,5Dimethylthiazol2yl)2,5diphenyl tetrazolium bromide assay, cell morphology was observed by inverted microscopy, and cell cycle progression and the mitochondrial membrane potential were analyzed using flow cytometry. The expression of Bcl2, Bax, p53, Cyclin D1 and cyclindependent kinase (CDK)2 proteins in BGC823 cells was analyzed with western blotting. The results demonstrated that DCA significantly inhibited cell growth, and that the cell cycle was arrested at the G1 phase. DCA was also shown to induce BGC823 cell apoptosis, which was associated with the collapse of the mitochondrial membrane potential. The mitochondriadependent pathway was activated via an increase in the ratio of Bax:Bcl2 in BGC823 cells. In addition, the expression of p53, cyclin D1 and CDK2 was altered following DCA treatment. These results suggest that DCA induces apoptosis in gastric carcinoma cells through activation of an intrinsic mitochondrialdependent pathway, in which p53 is involved.
Subject(s)
Antineoplastic Agents/pharmacology , Deoxycholic Acid/pharmacology , Signal Transduction/drug effects , Stomach Neoplasms/metabolism , Tumor Suppressor Protein p53/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Humans , Membrane Potential, Mitochondrial/drug effectsABSTRACT
The study aimed to evaluate the effects of deoxycholic acid (DCA) on human gastric carcinoma cell lines and to explore its mechanisms. In the present study, effects of DCA on SGC-7901 cell growth, cell cycle, and apoptosis were investigated by MTT assay, inverted microscopy, fluorescence microscopy, PI single- and FITC/PI double-staining flow cytometry, and western blotting. The study have revealed that DCA significantly inhibited the growth of SGC-7901 cells in a dose- and time-dependent manner and arrested cell cycle at G0/G1 phase. SGC-7901 cells showed typical apoptotic morphological changes after treated with DCA for 48 h. The intensity of typical apoptosis pattern- "ladders" formed by DNA in fragments of multiples of 200 base pairs was also observed. Apoptosis of SGC-7901 cells induced by DCA were associated with collapse of the mitochondrial membrane potential. DCA treatment could also increase the ratio of Bax to Bcl-2 in SGC-7901 cells. Meanwhile, the expression of p53, cyclinD1, and c-Myc were changed after DCA treatment. These results suggest that DCA induces apoptosis of gastric carcinoma cells through an intrinsic mitochondrial-dependent pathway, and the increase in the Bax/Bcl-2 ratio and collapse of the mitochondrial membrane potential may play important roles in DCA-induced apoptosis of gastric carcinoma cells.
