The natural flavone eupatorin induces cell cycle arrest at the G2/M phase and apoptosis in HeLa cells

Eupatorin (5,3′-dihydroxy-6,7,4′-trimethoxyflavone) is a natural flavone exhibiting antiproliferative activity in diverse cancer cell lines. In the present study, we characterized the cytotoxic effect of eupatorin in HeLa cervical carcinoma cells. Treatment with eupatorin induced cell cycle arrest at the G2/M phase within 12 h, followed by the induction of apoptosis. Eupatorin down-regulated cyclin D1 within 3 h, whereas up-regulated cyclin B1 levels after 12 h. Eupatorin also accumulated p53, p21, and Bax levels and stimulated the cleavage of caspase-3, caspase-7, and poly(ADP-ribose) polymerase after 12 h of treatment. In addition, we found that eupatorin-induced p21 expression was p53-dependent, while Bax expression was Egr-1-dependent pathway. Our results suggest that eupatorin induces G2/M cell cycle arrest through dysregulation of cell cycle regulatory proteins and triggers apoptosis through activation of the p53-dependent and p53-independent pathways.