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PU-H71 is a purine-scaffold Hsp90 inhibitor with less toxicity in normal cells than in cancer cells. In this study, we examined the in vitro radiosensitizing activity and molecular mechanisms of action of PU-H71 in human lung cancer cell lines. PU-H71 enhanced the sensitivity of the SQ-5 and A549 cancer cells to radiation. When the cancer cells were pre-treated with PU-H71, the repair of DNA double-strand breaks (DSBs) was markedly inhibited after irradiation compared with the cells that were not pre-treated with PU-H71, as evaluated by counting the foci of phosphorylated histone H2AX (γ-H2AX). We further demonstrated that post-irradiation, PU-H71 inhibited Rad51 foci formation, a critical protein for the homologous recombination pathway of DNA DSB repair. 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Radiosensitization of human lung cancer cells by the novel purine-scaffold Hsp90 inhibitor, PU-H71.
https://repo.qst.go.jp/records/46936
https://repo.qst.go.jp/records/4693667140fad-7ea2-40d1-befa-3b7b3ca59b56
Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2014-11-17 | |||||
タイトル | ||||||
タイトル | Radiosensitization of human lung cancer cells by the novel purine-scaffold Hsp90 inhibitor, PU-H71. | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
アクセス権 | ||||||
アクセス権 | metadata only access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
著者 |
Segawa, Tatsuya
× Segawa, Tatsuya× Fujii, Yoshihiro× Tanaka, Aya× Bando, Shin-Ichi× Okayasu, Ryuichi× Ohnishi, Ken× Kubota, Nobuo× 岡安 隆一 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | The molecular chaperone heat shock protein 90 (Hsp90) is involved in the maturation and stabilization of a wide range of oncogenic client proteins for oncogenesis and malignant cell proliferation, which renders this protein a promising target in the development of cancer therapeutics. PU-H71 is a purine-scaffold Hsp90 inhibitor with less toxicity in normal cells than in cancer cells. In this study, we examined the in vitro radiosensitizing activity and molecular mechanisms of action of PU-H71 in human lung cancer cell lines. PU-H71 enhanced the sensitivity of the SQ-5 and A549 cancer cells to radiation. When the cancer cells were pre-treated with PU-H71, the repair of DNA double-strand breaks (DSBs) was markedly inhibited after irradiation compared with the cells that were not pre-treated with PU-H71, as evaluated by counting the foci of phosphorylated histone H2AX (γ-H2AX). We further demonstrated that post-irradiation, PU-H71 inhibited Rad51 foci formation, a critical protein for the homologous recombination pathway of DNA DSB repair. These data indicate that targeting Hsp90 with PU-H71 may be novel therapeutic strategy for radioresistant carcinomas. | |||||
書誌情報 |
International journal of molecular medicine 巻 33, 号 3, p. 559-564, 発行日 2013-12 |
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ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 1107-3756 | |||||
PubMed番号 | ||||||
識別子タイプ | PMID | |||||
関連識別子 | 24366006 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | 10.3892/ijmm.2013.1594 |