Dihydromyricetin suppresses the proliferation of hepatocellular carcinoma cells by inducing G2/M arrest through the Chk1/Chk2/Cdc25C pathway.

The aim of the present study was to evaluate the antitumor mechanism of dihydromyricetin (DHM). Results showed that DHM significantly inhibited cell viability of HepG2 and Hep3B cells in a dose-dependent manner. DHM induced G2/M cell-cycle arrest in HepG2 and Hep3B cells by altering the expression of cell cycle proteins such as cyclin A, cyclin B1, Cdk1, p53, Cdc25c, p-Cdc25c Chk1 and Chk, which are critical for G2/M transition. Knockdown of p53 and Chk1 in HepG2 cells did not affect G2/M phase arrest caused by DHM. Furthermore, G2/M arrest induced by DHM can be disrupted by Chk2 siRNA. These findings indicate that DHM inhibits the growth of hepatocellular carcinoma (HCC) cells via G2/M phase cell cycle arrest through Chk1/Chk2/Cdc25C pathway. The present study identified effects of DHM in G2/M phase arrest in HCC and described detailed mechanisms of G2/M phase arrest by this agent, which may contribute to its overall cancer preventive efficacy in HCC.