Effect of iron chelator, hydroxyl radical scavenger and cytochrome P450 inhibitors on the cytotoxicity of cisplatin to tumor cells.
BACKGROUND
Iron catalyzed reactive oxygen metabolites (ROM) are important mediators in cisplatin (CP)-induced nephrotoxicity, and cytochrome P450 (CYP) is the major source of this iron. Iron chelators, hydroxyl radical scavengers and CYP inhibitors have shown marked protection.


METHODS
This study was designed to determine whether these agents affect the tumoricidal efficacy of CP to LLC-WRC 256 tumor cells.


RESULTS
CP was cytotoxic to the tumor cells in a dose and time dependent manner. Iron chelator, hydroxyl radical scavenger and CYP inhibitors did not reduce the cytotoxic effect of CP. Exposure of the tumor cells to CP did not increase the catalytic iron release and the generation of hydroxyl radical. Both CYP activity and content in the tumor cells were less than 10% of that in the rat liver.


CONCLUSIONS
We speculate that iron chelator, hydroxyl radical scavenger and CYP inhibitors do not alter the antitumor efficacy of CP.
Liu
H
H
Department of Pediatrics, Division of Nephrology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505, USA.
Baliga
R
R
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002279:Carcinoma 256, Walker / Q000188:drug therapy*; D016923:Cell Death; D002927:Cimetidine / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology*; D065607:Cytochrome P-450 Enzyme Inhibitors; D003676:Deferoxamine / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007502:Iron Chelating Agents / Q000494:pharmacology*; D010882:Piperonyl Butoxide / Q000494:pharmacology; D051381:Rats; D013997:Time Factors
D000970:Antineoplastic Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D007502:Iron Chelating Agents; D002927:Cimetidine; D003676:Deferoxamine; D010882:Piperonyl Butoxide; D002945:Cisplatin; D004121:Dimethyl Sulfoxide