Radiosensitization of human lung cancer cells by the novel purine-scaffold Hsp90 inhibitor, PU-H71

  • Authors:
    • Tatsuya Segawa
    • Yoshihiro Fujii
    • Aya Tanaka
    • Shin-Ichi Bando
    • Ryuichi Okayasu
    • Ken Ohnishi
    • Nobuo Kubota
  • View Affiliations

  • Published online on: December 19, 2013     https://doi.org/10.3892/ijmm.2013.1594
  • Pages: 559-564
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Abstract

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.
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2014-March
Volume 33 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Segawa T, Fujii Y, Tanaka A, Bando S, Okayasu R, Ohnishi K and Kubota N: Radiosensitization of human lung cancer cells by the novel purine-scaffold Hsp90 inhibitor, PU-H71. Int J Mol Med 33: 559-564, 2014.
APA
Segawa, T., Fujii, Y., Tanaka, A., Bando, S., Okayasu, R., Ohnishi, K., & Kubota, N. (2014). Radiosensitization of human lung cancer cells by the novel purine-scaffold Hsp90 inhibitor, PU-H71. International Journal of Molecular Medicine, 33, 559-564. https://doi.org/10.3892/ijmm.2013.1594
MLA
Segawa, T., Fujii, Y., Tanaka, A., Bando, S., Okayasu, R., Ohnishi, K., Kubota, N."Radiosensitization of human lung cancer cells by the novel purine-scaffold Hsp90 inhibitor, PU-H71". International Journal of Molecular Medicine 33.3 (2014): 559-564.
Chicago
Segawa, T., Fujii, Y., Tanaka, A., Bando, S., Okayasu, R., Ohnishi, K., Kubota, N."Radiosensitization of human lung cancer cells by the novel purine-scaffold Hsp90 inhibitor, PU-H71". International Journal of Molecular Medicine 33, no. 3 (2014): 559-564. https://doi.org/10.3892/ijmm.2013.1594