Preferential Sensitization of Tumor Cells to Radiation by Heat Shock Protein 90 Inhibitor Geldanamycin | Zendy

Yoshitaka Matsumoto | Zendy; Hikaru Machida | Zendy; Nobuo Kubota | Zendy

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Preferential Sensitization of Tumor Cells to Radiation by Heat Shock Protein 90 Inhibitor Geldanamycin

Author(s) -

Yoshitaka Matsumoto,

Hikaru Machida,

Nobuo Kubota

Publication year - 2005

Publication title -

journal of radiation research

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 0.643

H-Index - 60

eISSN - 1349-9157

pISSN - 0449-3060

DOI - 10.1269/jrr.46.215

Subject(s) - geldanamycin , hsp90 , sensitization , protein kinase b , heat shock protein , apoptosis , cancer research , pi3k/akt/mtor pathway , chemistry , microbiology and biotechnology , hsp90 inhibitor , biology , immunology , biochemistry , gene

The purpose of this study was to investigate the radiosensitizing effect of geldanamycin (GA), an inhibitor of heat shock protein 90, on tumour cells and normal cells. We tested the effect of a combination of GA and radiation on cell survival, PI3K/Akt-related proteins and apoptosis induction. GA sensitized tumour cells to radiation in preference to normal cells. In addition, a combination of radiation and GA abolished Akt activities and strongly enhanced the induction of apoptosis in tumour cells which depend on Akt protein activities for cell survival. The present data support the hypothesis that GA sensitizes tumour cells by modulating the balance among mitogenic, antiproliferative and apoptotic pathways. Targeting Hsp90 in tumour cells may lead to the development of new radiosensitizing strategies in radiotherapy.

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