Mechanistic studies of the apoptosis induced by the macrocyclic natural product tetrandrine in MGC 803 cells

Tetrandrine (Tet) is a macrocyclic tetrahydroisoquinoline alkaloid isolated from Stephania tetrandra S. Moore along with other Chinese and Japanese herbs. It has been used extensively for the treatment of silicosis, autoimmune disorders, inflammatory diseases and cardiovascular diseases. Of late, Tet has garnered increasing attention for its anticancer activity and its efficacy to reverse chemoresistance. In this study, we evaluated the cytotoxicity of Tet on MGC 803 gastric cancer cells using the methyl thiazolyl tetrazolium (MTT) assay. In addition, apoptosis and cell cycle were analyzed through flow cytometry, mitochondrial membrane potential (MMP) was measured using fluorescence microscopy and migration of cells was determined by transwell assay. It was observed that Tet efficiently inhibited the proliferation of MGC 803 cells in a concentration-dependent and time-dependent manner and reduced the number of colonies at low concentrations. It induced apoptosis through mitochondrial dysfunction, which may be related with upregulated Bcl-2-associated X protein (Bax), and downregulated of B cell lymphoma 2 (Bcl-2). On the other hand, Tet blocked the cell cycle at Gap 2 (G2)/mitosis (M) phase, which was associated with the upregulation of p21 CIP1/WAF1 . Furthermore, Tet elevated the intracellular reactive oxygen species (ROS) level and suppressed the migration of MGC 803 cells. Altogether, we demonstrated that Tet inhibited the proliferation and migration of gastric cancer MGC 803 cells and thus might be a potential drug candidate for the treatment of gastric cancer.