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.
Tian
Junqiang
J
Department of Radiation Oncology, Stanford University, Stanford, CA 94305, USA.
Peehl
Donna M
DM
Zheng
Wengwei
W
Knox
Susan J
SJ
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D015394:Molecular Structure; D010084:Oxidation-Reduction / Q000187:drug effects / Q000528:radiation effects; D010100:Oxygen / Q000378:metabolism; D011467:Prostate / Q000166:cytology / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D011838:Radiation-Sensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D013882:Thiosemicarbazones / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D007502:Iron Chelating Agents; D011838:Radiation-Sensitizing Agents; D013882:Thiosemicarbazones; C539263:di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone; D007501:Iron; D005978:Glutathione; D010100:Oxygen