Trans-1,3-diphenyl-2,3-epoxypropan-1-one, a chalcone derivative, induces apoptosis via ROS-mediated down-regulation of Bcl-xL in human leukemia HL-60 cells

摘要

The anticancer effects of trans-1,3-diphenyl-2,3-epoxypropan-1-one (DPEP), a chalcone derivative, were investigatedin human leukemia HL-60 cells. Treatment of HL-60 cells with various concentration of DPEP resultedin a sequence of events characteristic of apoptosis, including loss of cell viability, morphological changes, andincreased sub-G1 DNA content. We demonstrated that DPEP elevates reactive oxygen species (ROS) levels inHL-60 cells, and that the ROS scavenger N-acetylcysteine (NAC) could block DPEP-induced ROS generationand apoptosis. Western blot analysis revealed that DPEP inhibits Bcl-xL expression, leading to caspase-3 activationand poly-ADP-ribose polymerase (PARP) cleavage, thereby inducing apoptosis. However, NAC pretreatmentsignificantly inhibited the activation of caspase-3 and PARP cleavage and reduced Bcl-xL levels.These findings provide the first evidence that DPEP may inhibit the growth of HL-60 cells and induce apoptosisthrough a ROS-mediated Bcl-xL pathway.