Enhancement of radiation induced cell death in chicken B lymphocytes by withaferin A.
Withaferin A (WA), a plant withanolide, has shown significant radiosensitizing effect in vitro and in vivo. Inhibition of DNA repair has been suggested as a mechanism of radiosensitization by WA. To test this, the effect of withaferin A on survival of DT40 chicken B-lymphocyte cell line and its repair deficient single gene mutants Rad54-/-, Ku70-/- and double mutant Ku70-/- /Rad54-/- after irradiation was studied. Exponentially growing cells were treated for 1 hr with 5 microM WA and then exposed to different doses of X-rays. Cell survival was studied by clonogenic assay. WA significantly reduced survival of DT40, Ku70-/- and Ku70-/- /Rad54-/-, but not Rad54-/- cells, suggesting that WA enhances radiosensitivity by interfering with homologous repair, the major pathway of DSB repair in these cells. Inhibition of DNA repair is further indicated in a significant decrease in surviving fraction of DT40 cells by post-irradiation incubation with WA. This could have relevance to cancer radiotherapy.
Uma Devi
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Department of Radiation Biology, Research Reactor Institute, Kyoto University, Kumatori-cho, Osaka, Japan. devi_puma31@yahoo.com.sg
Utsumiz
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H
Takata
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Takeda
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D000818:Animals; D001402:B-Lymphocytes / Q000528:radiation effects*; D016923:Cell Death / Q000528:radiation effects; D002460:Cell Line; D002645:Chickens; D004260:DNA Repair / Q000187:drug effects* / Q000235:genetics / Q000528:radiation effects*; D004875:Ergosterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D009687:Nuclear Proteins / Q000235:genetics; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D054358:Withanolides; D014965:X-Rays / Q000009:adverse effects
D009687:Nuclear Proteins; D011838:Radiation-Sensitizing Agents; D054358:Withanolides; C009684:withaferin A; D004875:Ergosterol