The combination of venetoclax and quercetin exerts a cytotoxic effect on acute myeloid leukemia

Abstract Venetoclax is a BH3 mimetic and approved recently for Acute mteloid leukemia (AML) treatment. However, venetoclax’s effect on AML is still restrictive and a novel strategy is required. We demonstrate here for the first time that by a combination with a kind of naturally occurring flavonoid quercetin, the cytotoxic effect of venetoclax drastically increased. Combined treatment with venetoclax and quercetin changed most of AML cell KG-1 to a condensed morphology. Cell cycle analysis revealed that the combination strongly induced cell death. Caspase inhibitor blocked the cell death and the combination induced PARP cleavage, indicating that apoptosis was mainly induced. These effects were also observed in another AML cell Kasumi-1 but not in chronic myeloid leukemia (CML) cell K562. Public data analysis demonstrated that Bcl-2 expression is increased in AML cells compared to other malignant tumors and the survival and the growth of AML cell line depends on Bcl-2. Bcl-2/Bax ratio is a determining factor in whether or not to induce apoptosis. We found that quercetin increased Bax expression in KG-1. Our study provides a novel function of quercetin and a promising strategy for AML treatment using venetoclax