Cantharidin inhibits cell proliferation and induces apoptosis through G2/ME phase cell cycle arrest in hepatocellular carcinoma stem cells

The present study was designed to investigate the effect of cantharidin on cell proliferation, ability of self-renewal, cell cycle arrest and induction of apoptosis in HepG2 hepatocellular carcinoma stem cells (HCSCs). It was observed that cantharidin treatment exhibited dose- and time-dependent inhibitory effect on the viability of HCSCs. The inhibition of cell viability by cantharidin in HepG2 CD133(+) and parental cells was significant at the concentration 5 and 15 mu M, respectively after 48 h. Cantharidin treatment inhibited the self-renewal ability of the HCSCs and the expression of beta-catenin and cyclin D1. Flow cytometry revealed that cantharidin treatment at 5 mu M concentration significantly increased the cell population in G2/M phase and decreased the population in the G1 phase. Cantharidin treatment in the HCSCs for 48 h increased expression of histone H2AX, Myt1, cyclin A2, cyclin B1, p53 and cdc2 (Tyr15) phosphorylation significantly compared to the parental cells. Exposure of the HCSCs to cantharidin for 48 h at a concentration of 5 mu M caused a significant increase in the proportion of apoptotic cells. Therefore, cantharidin is a promising agent for the hepatocellular carcinoma treatment.