Abstract
INTRODUCTION: To examine the anti-cancer effects of berberine on multiple cancer cell lines, and to clarify the underlying molecular mechanisms. MATERIAL AND METHODS: The IC(50) values for the action of berberine on Tca8113 (oral squamous cell carcinoma), CNE2 (nasopharyngeal carcinoma cell), MCF-7 (breast cancer), Hela (cervical carcinoma), and HT29 (colon cancer) cells were determined by MTT cell viability assay. Early apoptosis and cell cycle arrest were examined by flow cytometry with annexin V and propidium iodide (PI) staining, respectively. For expression of BAX and BCL-2 genes and proteins were detected by real-time PCR and western blotting, respectively. RESULTS: Berberine displayed a cytotoxic effect on all the cell lines tested. The IC(50) values were determined (Tca8113, 218.52 ±18.71; CNE2, 249.18 ±18.14; MCF-7, 272.15 ±11.06; Hela, 245.18 ±17.33; and HT29, 52.37 ±3.45). PI staining revealed that berberine treatment resulted in cell cycle arrest at G2/M. The treatment also induced early apoptosis as shown by annexin V staining. In addition, berberine significant elevated gene and protein expression of BAX, which was accompanied by substantial decreases in BCL-2 gene and protein levels. The effects of berberine on BAX and BCL-2 were time-dependent. CONCLUSIONS: Berberine exhibited cytotoxic effects on multiple cancer cell lines by inducing apoptosis and cell cycle arrest. The BCL-2/BAX signaling pathway may be the common pathway underlying the anti-tumor effect of berberine. The findings support the notion that berberine is a dietary compound that can be further developed into a drug candidate for cancer treatment.