Anti-tumor and radiosensitization activities of the iron chelator HDp44mT are mediated by effects on intracellular redox status.

A novel iron chelator, HDp44mT, has been reported to have potent anti-proliferative effects on cancer cells; however, the underlying mechanism of action is not well understood. In this study, we characterized the cytotoxic effect of HDp44mT in a chemo- and radio-resistant cell line (PC-3) of prostatic cancer origin. The activity of HDp44mT at nM concentrations was dependent on the intracellular GSH and atmospheric O(2) concentration, rather than iron deprivation. HDp44mT also radiosensitized PC-3 cells in a GSH-dependent manner. Interestingly, this radiosensitizing effect was observed under aerobic and, to a larger extent, hypoxic conditions, suggesting its potential utility as a radiosensitizer for some radioresistant tumors.