Implication of intracellular ROS formation, caspase-3 activation and Egr-1 induction in platycodon D-induced apoptosis of U937 human leukemia cells

摘要: Abstract Platycodon D is a major constituent of triterpene saponins found in the root grandiflorum, Platycodi Radix, which widely used traditional Oriental medicine for treatment many chronic inflammatory diseases. The results previous studies have shown that this compound has vitro growth-inhibitory activity human cancer cells, however, mechanism by action occurs poorly understood. In study, we examined effects platycodon on production reactive oxygen species (ROS) and evaluated association these with apoptotic tumor cell death using leukemic U937 line. study demonstrate mediates ROS production, mediation followed decrease mitochondrial membrane potential (MMP, ΔΨm), activation caspase-3, cleavage poly (ADP-ribose) polymerase (PARP). Both cytotoxic characteristics induced were significantly inhibited z-DEVD-fmk, caspase-3 inhibitor, demonstrates important role plays observed effect. Additionally, transcription factor early growth response-1 (Egr-1) gene was transcriptionally activated levels non-steroidal anti-inflammatory drug (NSAID)-activated gene-1 (NAG-1) protein elevated D-treated cells. However, quenching generation response to scavenger, N-acetyl- l -cysteine, reversed D-induced apoptosis via inhibition Egr-1 activation, MMP collapse, subsequent caspase-3. Although further are needed increased expression leads directly NAG-1 induction apoptosis, our observations clearly indicate through involved molecular events pathway.