Apoptosis induced by cisplatin nephrotoxic injury.
An agent often used in cancer treatment, cisplatin may cause acute renal failure after even a single dose. Recent laboratory studies confirmed the induction of renal cell apoptosis by cisplatin. Reduction in cell viability as well as increase in the number of cells with fragmented nuclei correlated with cisplatin exposure in a dose-dependent manner. Gel electrophoresis revealed the presence of a characteristic laddering pattern which was preceded by an increase in caspase-3 activity. As the cisplatin concentration increased beyond 50 microM, the elevation of caspase-3 activity declined, which suggests that necrosis, instead of apoptosis, is more likely to be responsible for cell death secondary to higher cisplatin concentrations. Elucidation of the molecular mechanisms of cisplatin nephrotoxicity may lead to the development of a novel therapeutic strategy that targets cancer cell death while simultaneously minimizing renal injury.
Lau
A H
AH
University of Illinois at Chicago, 60612, USA.
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D020170:Caspase 1 / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D007668:Kidney / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D018374:LLC-PK1 Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D013552:Swine
D000970:Antineoplastic Agents; D053148:Caspase 3; D020169:Caspases; D020170:Caspase 1; D002945:Cisplatin