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Article

Targeting Mitochondria in Melanoma

1
Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria
2
Department of Dermatology and Allergology, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria
*
Authors to whom correspondence should be addressed.
Biomolecules 2020, 10(10), 1395; https://doi.org/10.3390/biom10101395
Received: 31 August 2020 / Revised: 23 September 2020 / Accepted: 28 September 2020 / Published: 30 September 2020
(This article belongs to the Special Issue Targeting Tumor Metabolism: From Mechanisms to Therapies)
Drastically elevated glycolytic activity is a prominent metabolic feature of cancer cells. Until recently it was thought that tumor cells shift their entire energy production from oxidative phosphorylation (OXPHOS) to glycolysis. However, new evidence indicates that many cancer cells still have functional OXPHOS, despite their increased reliance on glycolysis. Growing pre-clinical and clinical evidence suggests that targeting mitochondrial metabolism has anti-cancer effects. Here, we analyzed mitochondrial respiration and the amount and activity of OXPHOS complexes in four melanoma cell lines and normal human dermal fibroblasts (HDFs) by Seahorse real-time cell metabolic analysis, immunoblotting, and spectrophotometry. We also tested three clinically approved antibiotics, one anti-parasitic drug (pyrvinium pamoate), and a novel anti-cancer agent (ONC212) for effects on mitochondrial respiration and proliferation of melanoma cells and HDFs. We found that three of the four melanoma cell lines have elevated glycolysis as well as OXPHOS, but contain dysfunctional mitochondria. The antibiotics produced different effects on the melanoma cells and HDFs. The anti-parasitic drug strongly inhibited respiration and proliferation of both the melanoma cells and HDFs. ONC212 reduced respiration in melanoma cells and HDFs, and inhibited the proliferation of melanoma cells. Our findings highlight ONC212 as a promising drug for targeting mitochondrial respiration in cancer. View Full-Text
Keywords: melanoma; mitochondrial respiration; antibiotic; anti-parasitic drug; ONC212; Warburg effect; BRAF; NRAS melanoma; mitochondrial respiration; antibiotic; anti-parasitic drug; ONC212; Warburg effect; BRAF; NRAS
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MDPI and ACS Style

Aminzadeh-Gohari, S.; Weber, D.D.; Catalano, L.; Feichtinger, R.G.; Kofler, B.; Lang, R. Targeting Mitochondria in Melanoma. Biomolecules 2020, 10, 1395. https://doi.org/10.3390/biom10101395

AMA Style

Aminzadeh-Gohari S, Weber DD, Catalano L, Feichtinger RG, Kofler B, Lang R. Targeting Mitochondria in Melanoma. Biomolecules. 2020; 10(10):1395. https://doi.org/10.3390/biom10101395

Chicago/Turabian Style

Aminzadeh-Gohari, Sepideh, Daniela D. Weber, Luca Catalano, René G. Feichtinger, Barbara Kofler, and Roland Lang. 2020. "Targeting Mitochondria in Melanoma" Biomolecules 10, no. 10: 1395. https://doi.org/10.3390/biom10101395

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