Enhanced radiation induced cell killing by Herbimycin A pre-treatment

Noguchi, Miho; Hirayama, Ryoichi*; Druzhinin, S.*; Okayasu, Ryuichi*

Herbimycin A binds to conserved pockets of heat shock protein 90 (Hsp90) and inhibits its chaperone functions. Hsp90 plays an important role in tumor cell growth and survival though maintaining stability of proteins by its chaperone activity. It is known that some of the proteins associated with radio-resistance are functionally stabilized on Hsp90. In this study, we investigated the effect of herbimycin A on radiation sensitivity in human tumor cells and the mechanism related to the sensitization. For mechanistic insight, we examined repair of DNA double strand breaks (DSBs) in irradiated human cells pre-treated with herbimycin A. The lung squamous carcinoma cell cine, SQ-5, was used. Cells were treated with 1, 2, and 4 M herbimycin A for 24 h before X-irradiation. SQ-5 cells showed increased radiation sensitivity when pre-treated with herbimycin A. In addition, herbimycin A significantly inhibited repair of radiation induced DSBs. It is possible that one of the proteins associated with DNA DSB repair might be degraded by this drug as previously shown with another Hsp90 inhibitor 17-AAG, a geldanamycin derivative.