Quercetin induces oxidative stress and potentiates the apoptotic action of 2-methoxyestradiol in human hepatoma cells

Hepatocellular carcinoma (HCC) is the leading cause of cancer mortality in Asia. This study evaluated the growth inhibition effect of quercetin and 2-methoxyestradiol in vitro in human HCC cell lines. Combination treatment enhanced the cytotoxic effect in HA22T/VGH and HepG2 cell lines as compared with quercetin or 2-methoxyestradiol alone. The cell population of sub-G0/G1 phase and the level of annexin V binding were increased synergistically after combination treatment with quercetin and 2-methoxyestradiol in both cell lines. Moreover, quercetin combined with 2-methoxyestradiol increased superoxide levels, mitochondrial superoxide dismutase (MnSOD) in mRNA, protein levels, and SOD activity. Finally, we also found the mitochondrial membrane potential was decreased after combination treatment. The changes of reactive oxygen species and mitochondrial disruption were likely to be involved in the mechanism for the synergistic cytotoxicity effects of combination treatment in human hepatoma cells. These results provided a basis for further study of the potential usage of quercetin combination with hormonal agents for the treatment of human hepatoma.