Wogonin induces G1 phase arrest through inhibiting Cdk4 and cyclin D1 concomitant with an elevation in p21Cip1 in human cervical carcinoma HeLa cells

Wogonin, a naturally occurring flavonoid, has been shown to have tumor therapeutic potential both in vitro and in vivo. To better understand its anticancer mechanism, we examined the effect of wogonin on human cervical carcinoma HeLa cells. In this study, we observed that G(1) phase arrest was involved in wogonin-induced growth inhibition in HeLa cells. Over a 24 h exposure of HeLa cells to 90 mu mol.L-1 wogonin, the promoters of G(1)-S transition, including cyclin D1/Cdk4 and pRb, decreased within 12 h and E2F-1 depleted in the nucleus at the same time. As the G(1) phase arrest developed, p53 and the Cdk inhibitor p21(Cip1) elevated both at protein and mRNA levels. Furthermore, the up-regulation of p21(Cip1) induced by wogonin was dramatically inhibited by siRNA-mediated p53 gene silencing. Collectively, our data suggested that wogonin induced G(1) phase arrest in HeLa cells by modulating several key G(1) regulatory proteins, such as Cdk4 and cyclin D1, as well as up-regulation of a p53-midiated p21(Cip1) expression. This mechanism of wogonin may play an important role in the killing of cancerous cells and offer a potential mechanism for its anticancer action in vivo.