RT Journal Article SR Electronic T1 Berberine Induces Apoptosis in Human HSC-3 Oral Cancer Cells via Simultaneous Activation of the Death Receptor-mediated and Mitochondrial Pathway JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 3371 OP 3378 VO 27 IS 5A A1 LIN, CHIN-CHUNG A1 YANG, JAI-SING A1 CHEN, JIN-TANG A1 FAN, SHANG A1 YU, FU-SHUN A1 YANG, JIUN-LONG A1 LU, CHI-CHENG A1 KAO, MING-CHING A1 HUANG, AN-CHENG A1 LU, HSU-FENG A1 CHUNG, JING-GUNG YR 2007 UL http://ar.iiarjournals.org/content/27/5A/3371.abstract AB Evidence has accumulated that berberine is able to induce cell cycle arrest and apoptosis in many human cancer cell lines. However, there is no available information on the effects of berberine on human oral squamous cell carcinoma. In this study, the effects of berberine on cell growth, apoptosis and cell cycle regulation in human oral squamous carcinoma HSC-3 cells were examined. Berberine induced dose- and time-dependent irreversible inhibition of cell growth and cellular DNA synthesis. This was also confirmed by phase-contrast 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 correlated with caspase-3 activation. Flow cytometric studies of the cell cycle distribution showed that berberine induced mainly G0/G1-phase arrest. Flow cytometric examinations also showed that berberine induced reactive oxygen species (ROS) and Ca2+ production, as well as the dysfunction of mitochondrial membrane potential (MMP), which were correlated with apoptosis. In conclusion, our data support that berberine initially induces an endoplasmic reticulum stress response based on ROS and Ca2+ production which is followed by dysfunctions of the mitochondria, resulting in apoptosis of these oral cancer HSC-3 cells. Prolonged exposure of the HSC-3 cells to berberine causes increased apoptosis through reduced levels of MMP, release of cytochrome c and activation of caspase-3. Copyright© 2007 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved