Combination of withaferin A and X-ray irradiation enhances apoptosis in U937 cells

Abstract

Combined treatment with radiation has improved the outcome in various cancers and many radiosensi- tizers are used to enhance the therapeutic efficiency of radiotherapy.Withaferin A (Wit A), a natural com- pound derived from the medicinal plant Withania somnifera, has been reported for its anti-inflammatory and anti-tumor effects. In this study, we show that Wit A enhances the ionizing radiation (IR)-induced apoptosis in human lymphoma U937 cells. Wit A-enhanced IR-induced apoptosis is associated with the PARP cleavage, caspase-3 activation, as well as specifically down-regulation of anti-apoptotic protein Bcl-2, suggesting that Wit A may be useful as a potential radiosensitizer. In addition, pretreatment of U937 cells with SP600125 (JNK inhibitor) or SB203589 (p38 MAPK inhibitor) dose-dependently inhibited the proteolytic cleavage of PARP.We provide the evidence here that generation of reactive oxygen species (ROS), Bcl-2 down-regulation and activation of MAPKs pathway are critically involved in the apoptosis induced by Wit A and radiation. 2011 Published by Elsevier Ltd. Keywords: Withaferin A Radiation Apoptosis Reactive oxygen species Bcl-2