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• W1585962064 abstract "The purpose of the present study was to elucidate the radiosensitization caused by #946;-lapachone, a novel anti-cancer drug. FSaII fibrosarcoma of C3H mice and A549 human lung cancer cells were used. Cells were exposed to a single or split-dose irradiation with or without #946;-lapachone treatment and the clonogenic cell survival was determined. The effect of #946;-lapachone on the radiation-induced DNA double strand breaks was studied with #947;-H2AX method, and that on the radiation induced activation of NF-kB was determined. Molecular signals involved in cell death were studied with western blot analysis. Treating the cells with #946; -lapachone for 2 h, starting immediately before irradiation, markedly increased the radiosensitivity of the cells as indicated by significant change in the shoulder and the slop of the radiation survival curve of the cells. #946;-Lapachone suppressed the repair of sublethal radiation damage, as determined with split-dose irradiation method. Upon an exposure to 2 Gy irradiation, #947;-H2AX expression, hallmark of DNA double strand breaks, marked increased till 2 h post-irradiation and declined, and #946;-Lapachone significantly delayed the decay of #947;-H2AX, indicating that #946;-lapachone inhibited the repair of radiation-induced DNA double strand breaks. #946;-lapachone inhibited the radiation-induced phosphorylation of IkB-#945;, thereby inhibiting the activation of NF-kB. Phosphorylation of JNK by combination of #946;-lapachone and irradiation was significantly greater than that caused by either of them alone. All these interaction between #946;-lapachone and radiation could be reduced when cells were transfected with shNQO1, demonstrating that NQO1 plays critical role in the radiosensitization caused by #946; -lapachone. Conclusion: #946; -lapachone sensitizes cancer cells to radiation by inhibiting repair of DNA double strand breaks in NQO1 dependent manner. Acknowledgments: This work supported by grants of National Nuclear Technology Program (2007) from KOSEF, the Korea Health 21 RD 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2308." @default.
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• W1585962064 date "2009-05-01" @default.
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• W1585962064 title "Abstract #2308: Radiosensitization of cancer cells by #946;-lapachone" @default.
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