Histone hyperacetylation is involved in the quercetin-induced human leukemia cell death.

Quercetin (QU) is recognized as a promising anticancer drug, but its mechanism remains elusive. Here we found that QU induced human leukemia cell death in a dose-dependent manner. However, it did not show a dose-dependent inhibition on ROS generation (indicated by the level of malondialdehyde, MDA) in the same cells. QU showed similar antioxidant activity at concentrations of 50, 75 and 100 microM. Consistent with that, the antioxidant, N-acetyl-cysteine (NAC) could only further decrease the ROS generation and enhance the cell death triggered by QU at the concentrations less than 50 microM. These results indicate that an additional mechanism is involved in the anticancer activity of high concentrations of QU. When the effect of QU on histone acetylation was studied, QU induced significant histone hyperacetylation at 75 and 100 microM, indicating the possible involvement of histone hyperacetylation in the anticancer activity of high concentrations of QU. This conclusion was supported by the findings that when histone acetylation in the cells treated by QU was increased by different concentrations of TSA, the cell death was significantly enhanced. Our results thus provide the first evidence that QU can induce histone hyperacetylation and this induction of histone hyperacetylation may represent an unrevealed mechanism in its anticancer activity.