Abstract
Resistance to apoptosis is an characteristic of cancer cells that serves a critical function in tumor development and represents a target for antitumor therapy. Isoimperatorin (ISOIM), a coumarin compound, exhibits antitumor functions in multiple types of tumor cells. However, its antitumor effects and molecular mechanisms with respect to gastric cancer have not been elucidated. The present study assessed the anti-proliferative and apoptotic effects of ISOIM on human BGC-823 gastric cancer cells and elucidated its underlying molecular mechanisms. Cell proliferation was evaluated using MTT assays. Analysis of cell morphology was performed by hematoxylin and eosin, Hoechst 33258 and acridine orange/ethidium bromide staining. In addition, cell cycle and apoptosis was evaluated using flow cytometry analysis; expression of apoptosis-associated proteins was studied by western blotting. The results of the present study revealed that ISOIM significantly inhibited cell proliferation by arresting the cell cycle at the G2/M phase and induced apoptosis by increasing Bcl-2-associated X (Bax) expression with a concomitant decrease in Bcl-2 expression, resulting in a decreased Bcl-2/Bax ratio compared with the control. In addition, ISOIM treatment also resulted in cytochrome c translocating from the mitochondria to the cytosol. Furthermore, caspase-3 was significantly activated in response to treatment with ISOIM, suggesting that apoptosis in BGC-823 cells is induced in the mitochondrial pathway. Taken together, the results of the present study indicate that ISOIM may significantly induce apoptosis in BGC-823 cells and that the pro-apoptotic mechanisms of ISOIM could be associated with the mitochondrial pathway.