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

Segawa,Tatsuya; Fujii,Yoshihiro; Tanaka,Aya; Bando,Shin-Ichi; Okayasu,Ryuichi; Ohnishi,Ken; Kubota,Nobuo

doi:10.3892/ijmm.2013.1594

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
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Affiliations: Department of Radiological Sciences, Center for Humanity and Arts, Ibaraki Prefectural University of Health Sciences, Ami-machi, Inashiki-gun, Ibaraki 300-0394, Japan, Department of Biology, Center for Humanity and Arts, Ibaraki Prefectural University of Health Sciences, Ami-machi, Inashiki-gun, Ibaraki 300-0394, Japan, Heavy-ion Radiobiology Group, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Inage-ku, Chiba 263-8555, Japan
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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