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Functional impairment induced by lipophilic cationic compounds on mitochondria
1Ontario Cancer Foundation, Hamilton Regional Cancer Centre, Ont., Canada.
Canadian Journal of Physiology and Pharmacology
|March 1, 1988
Summary
Lipophilic cations like rhodamine 123 show anticancer effects by impacting mitochondrial function. These compounds inhibit mitochondrial respiration and affect oxidative phosphorylation similarly.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Lipophilic cations, including rhodamine 123, exhibit selective anticarcinoma activity against epithelial-derived tumor cells and in vivo models.
- The precise mechanisms underlying the effects of these compounds on mitochondrial function require further elucidation.
Purpose of the Study:
- To investigate the mechanism by which rhodamine 123 and safranin influence mitochondrial function.
- To compare the effects of rhodamine 123 and safranin on mitochondrial respiration and oxidative phosphorylation.
Main Methods:
- Mitochondrial respiration was measured using substrates like succinate and ascorbate plus tetramethylphenylenediamine.
- The effect of lipophilic cations on ADP-stimulated mitochondrial respiration was assessed.
- ATP hydrolysis rates were measured at varying concentrations of lipophilic cations.
Main Results:
- Rhodamine 123 and safranin demonstrated similar inhibitory effects on ADP-stimulated mitochondrial respiration.
- This inhibition was observed irrespective of the respiratory substrate used.
- High concentrations of lipophilic cations led to a twofold stimulation of ATP hydrolysis.
Conclusions:
- Rhodamine 123 and safranin exert similar effects on mitochondrial oxidative phosphorylation.
- These findings provide insight into the mechanism of action for lipophilic cations with anticarcinoma properties.