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

Authors
Yang, ES; Choi, MJ; Kim, JH; Choi, KS; Kwon, TK
Citation
Toxicology in vitro : an international journal published in association with BIBRA, 25(8):1803-1810, 2011
Journal Title
Toxicology in vitro : an international journal published in association with BIBRA
ISSN
0887-23331879-3177
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.
MeSH terms
Antineoplastic Agents, Phytogenic/*pharmacology*Apoptosis/drug effects/radiation effectsCombined Modality TherapyDown-RegulationHumansJNK Mitogen-Activated Protein Kinases/metabolismLymphoma, Large B-Cell, Diffuse/*drug therapy/metabolism/*radiotherapyProto-Oncogene Proteins c-bcl-2/metabolismReactive Oxygen Species/metabolismU937 CellsWithanolides/*pharmacology*X-Ray Therapyp38 Mitogen-Activated Protein Kinases/metabolism
DOI
10.1016/j.tiv.2011.09.016
PMID
21964475
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
AJOU Authors
최, 경숙
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