Berberine Induces Apoptosis and Arrests Cell Cycle in Multiple Cancer Cell lines

Abstract

IntroductionTo examine the anti-cancer effects of berberine on multiple cancer cell lines; and to clarify the underlying molecular mechanisms.Material and methodsThe IC50 values 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 was examined by flow cytometry with annexin V and propidium iodide (PI) staining, respectively. For expressions of BAX and BCL-2 genes and proteins were detected by real-time PCR and western blotting, respectively.ResultsBerberine displayed cytotoxic effect on all the cell lines tested. The IC50 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 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.ConclusionsBerberine 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.