Berberine induces cell cycle arrest and apoptosis in human HSC-3 oral cancer cells

Evidence has accumulated that berberine induced cell cycle arrest and apoptosis in many human cancer cell lines. However, there is no available information to address berberine affecting human oral quamous carcinoma cancer HSC-3 cells. In this study, we have examined the effects of berberine on cell growth and apoptosis and cell cycle regulation in human oral squamous carcinoma HSC-3 cells. Berberine induced dose- and time-dependent of irreversible inhibition of cell growth and cellular DNA synthesis. It was also confirmed by phase-light microscopy which showed that berberine induced morphological changes in HSC-3 cells. Propidium iodide/annexin V staining for flow cytometric analysis showed that berberine induced apoptosis correlating with caspase-3 activation in examined cells. Flow cytometry studies of the cell cycle distribution showed that berberine induced mainly G0/G1-phase arrest. Flow cytometry examinations also showed that berberine induced reactive oxygen species (ROS) and Ca2+ production and dysfunction of mitochondrial membrane potential (MMP) which are correlated with apoptosis. In conclusion, our data supports a view that berberine initially induces an endoplasmic reticulum stress response based on ROS and Ca2+ production then followed by dysfunction mitochondria, resulting in apoptosis of these oral cancer HSC-3 cells. Prolonged exposure of the HSC-3 cells to berberine causes increased percentage of apoptosis through decreased levels of MMP, cytochrome c release and activation of caspase-3.