Acetyl derivate of quercetin increases the sensitivity of human leukemia cells toward apoptosis

Abstract

The hydroxyl groups of flavonoids are important for their bioactive functions and also prone to oxidation to quinones. To block the potential oxidation of quercetin, and generate a stronger bioactive compound, we synthesized acetyl and methyl derivatives of quercetin, 3,7,3',4'-O-tetraacetylquercetin (4Ac-Q) and 3,7,3',4'-O-tetramethylquercetin (4Me-Q), which substituted the hydroxyl groups of quercetin with acetyl or methyl groups at the 3,7,3',4' positions of quercetin, and then evaluated the ability to cause cell proliferation inhibition and apoptosis in HL-60 cells. The results revealed that 4Ac-Q and quercetin, but not 4Me-Q, significantly inhibit cell proliferation by caspase-mediated apoptosis when characterized by DNA fragmentation, activation of caspase-3 and PARP cleavage while 4Me-Q lost this ability. Interestingly, 4Ac-Q revealed stronger apoptotic activity than parent quercetin via a ROS-independent pathway. These findings provide a valuable strategy to increase the sensitivity of human leukemia HL-60 cells toward apoptosis by modifying quercetin structure.