Abstract B70: Berberine, a putative bioactive compound from traditional herbal plant, induces apoptosis in MCF‐7 breast cancer cells through p53 activation and mitochondrion‐dependent pathway

Plant bioactive compounds found in many plant species have been used in Chinese, Unani, and Indian ayurvedic medicine. Accumulative evidences in both in vitro and in vivo studies using berberine seem to play anti‐cancer and anti‐inflammatory roles in different cancer cells. Previous research suggested berberine to exhibit potential anticancer activities in the various cancer cell lines. In the present study, we have isolated a putative compound from Phellodendron amurense using methanol and purified by chromatographic techniques. The structure of the isolated compound was identified as berberine by 2D NMR and mass spectral data. The isolated berberine was tested against MCF‐7 breast cancer cell line and the MCF‐12f normal breast epithelial cell line for 24, 48 and 72h at various concentrations (0, 12.5, 25, 50, 100, and 200µM). Using the MTT cell viability assay, berberine has demonstrated a significant cytotoxic effect on the MCF‐7 cell line (p <0.05) in a time and concentration dependent manner. However, the same alkaloid did not show an effect on the proliferation of the MCF‐12f normal cells. The induction of apoptosis or debilitation of cancer cells without causing excessive damage to normal cells by any natural putative compound is a key target for identifying methods of cancer prevention and therapy. Based on these results, MCF‐7 cells treated with 25µM berberine for 48 and 72h were used for further studies to illustrate a time dependent induction of apoptosis with flow cytometry and agarose gel electrophoresis to identify visible DNA fragmentation. Western blotting with treated cells revealed that berberine induces apoptosis in MCF‐7 cells through a mitochondrion‐dependent pathway by increasing levels of pro‐apoptotic protein, Bax, cytoplasmic cytochrome c, caspase‐9 activity and cleavage of PARP while decreasing levels of anti‐apoptotic protein, Bcl‐2. Immunoblotting also suggests that p53 plays a pro‐apoptotic role in berberine treated cells. We conclude that berberine inhibits the proliferation of MCF‐7 breast cancer cells through an apoptotic pathway which may serve as a potential compound for cancer prevention or therapy. Further studies are needed to elucidate specific mechanism of action of this putative compound in breast cancer cells.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):B70.