Modulation of Apoptosis by Berberine through Inhibition of Cyclooxygenase-2 and Mcl-1 Expression in Oral Cancer Cells

Abstract

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.