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Withaferin A enhances radiation-induced apoptosis in Caki cells through induction of reactive oxygen species, Bcl-2 downregulation and Akt inhibition.

Authors
Yang, ES; Choi, MJ; Kim, JH; Choi, KS; Kwon, TK
Citation
Chemico-biological interactions, 190(1):9-15, 2011
Journal Title
Chemico-biological interactions
ISSN
0009-27971872-7786
Abstract
Withaferin A (Wit A), a natural compound derived from the medicinal plant Withania somnifera, has been reported for the anti-tumor effects, including the inhibition of tumor cell growth, metastasis and angiogenesis. In this study, we investigated the effect of Wit A on radiation-induced apoptosis in human renal cancer cells (Caki cells). Our results showed that, compared with Wit A or radiation alone, the combination of both resulted in a significant enhancement of apoptosis, showing the increase in the cleavage of caspase-3 and PARP as well as sub-G1 cell population. In addition, reactive oxygen species (ROS) generation was correlated with the enhancement of radiation-induced apoptosis by Wit A. Wit A downregulated Bcl-2 protein levels and ectopic expression of Bcl-2 in Caki cells attenuated the apoptosis induced by Wit A plus radiation. Taken together, these results indicate that Wit A enhanced radiation-induced apoptosis in Caki cells through ROS generation, down-regulation of Bcl-2 and Akt dephosphorylation. Thus, our study shows that Wit A may be used as an effective radiosensitizer in cancer therapy.
MeSH terms
Antineoplastic Agents/chemistry/*pharmacology*ApoptosisCaspase 3/metabolismCell Line, TumorG1 PhaseHumansPlants, Medicinal/chemistryPoly(ADP-ribose) Polymerases/metabolismProto-Oncogene Proteins c-akt/*metabolismProto-Oncogene Proteins c-bcl-2/*metabolism*Radiation, IonizingReactive Oxygen Species/*metabolismWithania/chemistryWithanolides/chemistry/*pharmacology
DOI
10.1016/j.cbi.2011.01.015
PMID
21256832
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
AJOU Authors
최, 경숙
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