Anti-proliferative effect of isorhamnetin on HeLa cells through inducing G2/M cell cycle arrest

Abstract

As a major cancer type in females, cervical cancer has been explored in depth by researchers. HeLa is a cervical cancer cell line. Isorhamnetin is an O-methylated flavonol that is primarily extracted from sea buckthorn. In the present study, the anti-proliferative effect of isorhamnetin on HeLa cells was evaluated using a Trypan blue dye exclusion assay. Isorhamnetin inhibited the cell proliferation in a time- and dose-dependent manner. Flow cytometric analysis of the cell cycle distribution revealed that isorhamnetin inhibited the cell cycle progression of HeLa by causing G2/M phase arrest and decreasing the proportion of cells in G1 phase. In addition, western blot analysis was performed to evaluate the presence of certain cell cycle-associated proteins. It was demonstrated that isorhamnetin inhibited the protein expression of cyclin B1, cell division cycle 25C (Cdc25C) and Cdc2, but enhanced checkpoint kinase 2 (Chk2), Cdc25C and Cdc2 phosphorylation. In addition, tubulin depolymerization participated in the isorhamnetin-induced cell cycle arrest in G2/M phase. In conclusion, the present results indicated that the anti-proliferative action of isorhamnetin is associated with arrest of the cell cycle in G2/M phase, which is a consequence of activation of the ataxia telangiectasia mutated Chk2 pathway and disruption of microtubule function.