Energetic characteristics of cisplatin resistant ovarian carcinoma cells.
An elevated mitochondrial membrane potential coincides with cisplatin resistance in the 2008, C13* and RH4 ovarian carcinoma cell system. Since the mitochondrial membrane potential is a component of the overall proton motive force which drive mitochondrial ATP production, we evaluated the energetic characteristics of these cells with biochemical and pharmacologic assays. Our data shows that the cisplatin resistant C13* cells have reduced mitochondrial respiratory function and enhanced sensitivity to oligomycin, a specific inhibitor of oxidative phosphorylation, compared to the cisplatin sensitive 2008 parental line. This suggests that the chronic cisplatin exposures used to generate C13* cells debilitated mitochondrial functions. This characteristic, however, seems unrelated to cisplatin resistance since the impairment persist in the RH4 variant despite its returned cisplatin sensitivity. We suggest that mitochondrial membrane potential influences cellular processes distinct from energy production and that these processes are relevant to cisplatin resistance.
Dorward
A M
AM
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Singh
G
G
D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004734:Energy Metabolism; D005260:Female; D006019:Glycolysis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism*
D002945:Cisplatin