Enhanced Radiation Induced Cell Killing by Herbimycin A Pre-treatment

Herbimycin A (HA), as in Geldanamycin, binds to conserved pockets of heat shock protein 90 (Hsp90) and inhibits its chaperone functions. Hsp90 plays an important role in cancer cell growth and survival through maintaining stability of several proteins by its chaperones activity. It is known that some of the proteins associated with radiation responses are functionally stabilized by Hsp90. In this study, we investigated the effect of HA on radiosensitivity in human cancer cells and the mechanism related to the sensitization. For mechanistic insight of sensitization, we examined repair of DNA double strand breaks (DSBs) in irradiated human cancer cells pre-treated with HA; DSBs are thought to be the critical target for radiation-induced cell death. Cellular radiosensitivity was determined by clonogenic assay, and the DSB rejoining kinetics was examined by constant field gel electrophoresis. SQ-5, a lung squamous carcinoma cell line, showed synergistic increase in radiosensitivity when cells were pre-treated with HA. In addition, HA significantly inhibited repair of radiation induced DSBs. The results suggest that the combination of HA and ionizing radiation may be a useful therapeutic strategy in treating certain cancer cells.The 2nd Asia-Pacific Symposium on Radiation Chemistry (APSRC-2008