Modulation of apoptosis by berberine through inhibition of cyclooxygenase-2 and Mcl-1 expression in oral cancer cells.

BACKGROUND We have previously shown that berberine exerts its anti-inflammatory effects through inhibition of cyclooxygenase-2 (COX-2) expression. In this study, we explored the biochemical influence of berberine-induced COX-2 reduction and apoptosis. MATERIALS AND METHODS KB cells were treated with berberine, and the apoptosis was measured by morphology and caspase-3 activity. The effects of prostaglandin E2 (PGE2) on berberine-mediated cell growth were also determined. The expression of COX-2, Bcl-2, Mcl-1, Akt and phosphorylated Akt in berberine-treated KB cells, with or without PGE2, were assessed by Western blots. RESULTS Berberine induced apoptosis in KB cells, and was partially reversed by incorporation of PGE2. Berberine treatment inhibited COX-2 and Mcl-1 expression dose-dependently, but not Bcl-2. PGE2 induced COX-2 and Mcl-1 expression and reversed the repressive effect of berberine on Mcl-1. In addition, PGE2 had no effect on total Akt, but slightly reversed the phosphorylated Akt, which was decreased by berberine. CONCLUSION These results suggest that berberine-induced apoptosis might be COX-2-dependent and is related to decreased Akt phosphorylation and Mcl-1 expression.