title: 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 radiosensitizers are used to enhance the therapeutic efficiency of radiotherapy. Withaferin A (Wit A), a natural compound 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.
authors.affiliation: Department of Immunology, School of Medicine, Keimyung University, Daegu, South Korea.
authors.forename: Eun Sun
authors.initials: ES
authors.lastname: Yang
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Choi
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Kim
authors.forename: Kyeong Sook
authors.initials: KS
authors.lastname: Choi
authors.forename: Taeg Kyu
authors.initials: TK
authors.lastname: Kwon
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D015536:Down-Regulation; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020298:U937 Cells; D054358:Withanolides / Q000494:pharmacology*; D014964:X-Ray Therapy; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D054358:Withanolides; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C009684:withaferin A