Functional impairment induced by lipophilic cationic compounds on mitochondria.
Lipophilic cations, such as rhodamine 123, have selective anticarcinoma activity both in epithelial-derived tumor cells and in tumor cells injected into mice. The mechanism by which rhodamine 123 and safranin have their effect on mitochondrial function was examined. Rhodamine 123 and safranin inhibit the stimulation of mitochondrial respiration by ADP in a similar concentration range. This inhibition occurs whether the mitochondria are respiring on succinate as a substrate or on ascorbate plus tetramethylphenylenediamine. ATP hydrolysis was stimulated twofold by high lipophilic cation concentration. These results demonstrate that rhodamine 123 and safranin affect oxidative phosphorylation in a similar fashion.
Singh
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Ontario Cancer Foundation, Hamilton Regional Cancer Centre, Ont., Canada.
Shaughnessy
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SG
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D005456:Fluorescent Dyes / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010619:Phenazines / Q000494:pharmacology*; D020112:Rhodamine 123; D012235:Rhodamines / Q000494:pharmacology*; D014966:Xanthenes / Q000494:pharmacology*
D005456:Fluorescent Dyes; D010619:Phenazines; D012235:Rhodamines; D014966:Xanthenes; D020112:Rhodamine 123; D000251:Adenosine Triphosphatases; C009195:safranine T