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Multifaceted Roles of Mitochondrial Components and Metabolites in Metabolic Diseases and Cancer
Article

Involvement of Mitochondrial Mechanisms in the Cytostatic Effect of Desethylamiodarone in B16F10 Melanoma Cells

1
Department of Biochemistry and Medical Chemistry, University of Pécs Medical School, 7624 Pecs, Hungary
2
Szentagothai Research Centre, University of Pécs, 7624 Pecs, Hungary
3
HAS-UP Nuclear-Mitochondrial Interactions Research Group, 1245 Budapest, Hungary
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(19), 7346; https://doi.org/10.3390/ijms21197346
Received: 31 August 2020 / Revised: 29 September 2020 / Accepted: 1 October 2020 / Published: 5 October 2020
(This article belongs to the Special Issue Mitochondria-Targeted Approaches in Health and Disease)
Previously, we showed that desethylamiodarone (DEA), a major metabolite of the widely used antiarrhythmic drug amiodarone, has direct mitochondrial effects. We hypothesized that these effects account for its observed cytotoxic properties and ability to limit in vivo metastasis. Accordingly, we examined DEA’s rapid (3–12 h) cytotoxicity and its early (3–6 h) effects on various mitochondrial processes in B16F10 melanoma cells. DEA did not affect cellular oxygen radical formation, as determined using two fluorescent dyes. However, it did decrease the mitochondrial transmembrane potential, as assessed by JC-1 dye and fluorescence microscopy. It also induced mitochondrial fragmentation, as visualized by confocal fluorescence microscopy. DEA decreased maximal respiration, ATP production, coupling efficiency, glycolysis, and non-mitochondrial oxygen consumption measured by a Seahorse cellular energy metabolism analyzer. In addition, it induced a cyclosporine A–independent mitochondrial permeability transition, as determined by Co2+-mediated calcein fluorescence quenching measured using a high-content imaging system. DEA also caused outer mitochondrial membrane permeabilization, as assessed by the immunoblot analysis of cytochrome C, apoptosis inducing factor, Akt, phospho-Akt, Bad, and phospho-Bad. All of these data supported our initial hypothesis. View Full-Text
Keywords: amiodarone; apoptosis; metastatic melanoma; mitochondrial fusion-fission; mPT; Bad; Akt; Aif amiodarone; apoptosis; metastatic melanoma; mitochondrial fusion-fission; mPT; Bad; Akt; Aif
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MDPI and ACS Style

Ramadan, F.H.J.; Szabo, A.; Kovacs, D.; Takatsy, A.; Bognar, R.; Gallyas, F., Jr.; Bognar, Z. Involvement of Mitochondrial Mechanisms in the Cytostatic Effect of Desethylamiodarone in B16F10 Melanoma Cells. Int. J. Mol. Sci. 2020, 21, 7346. https://doi.org/10.3390/ijms21197346

AMA Style

Ramadan FHJ, Szabo A, Kovacs D, Takatsy A, Bognar R, Gallyas F Jr., Bognar Z. Involvement of Mitochondrial Mechanisms in the Cytostatic Effect of Desethylamiodarone in B16F10 Melanoma Cells. International Journal of Molecular Sciences. 2020; 21(19):7346. https://doi.org/10.3390/ijms21197346

Chicago/Turabian Style

Ramadan, Fadi H.J., Aliz Szabo, Dominika Kovacs, Aniko Takatsy, Rita Bognar, Ferenc Gallyas Jr., and Zita Bognar. 2020. "Involvement of Mitochondrial Mechanisms in the Cytostatic Effect of Desethylamiodarone in B16F10 Melanoma Cells" International Journal of Molecular Sciences 21, no. 19: 7346. https://doi.org/10.3390/ijms21197346

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