PloS one, 2012-08, Vol.7 (8), p.e40690-e40690
2012
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- Autor(en) / Beteiligte
- Titel
- Mitochondrial respiration--an important therapeutic target in melanoma
- Ist Teil von
- PloS one, 2012-08, Vol.7 (8), p.e40690-e40690
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2012
- Quelle
- Elektronische Zeitschriftenbibliothek (Open access)
- Beschreibungen/Notizen
- The importance of mitochondria as oxygen sensors as well as producers of ATP and reactive oxygen species (ROS) has recently become a focal point of cancer research. However, in the case of melanoma, little information is available to what extent cellular bioenergetics processes contribute to the progression of the disease and related to it, whether oxidative phosphorylation (OXPHOS) has a prominent role in advanced melanoma. In this study we demonstrate that compared to melanocytes, metastatic melanoma cells have elevated levels of OXPHOS. Furthermore, treating metastatic melanoma cells with the drug, Elesclomol, which induces cancer cell apoptosis through oxidative stress, we document by way of stable isotope labeling with amino acids in cell culture (SILAC) that proteins participating in OXPHOS are downregulated. We also provide evidence that melanoma cells with high levels of glycolysis are more resistant to Elesclomol. We further show that Elesclomol upregulates hypoxia inducible factor 1-α (HIF-1α), and that prolonged exposure of melanoma cells to this drug leads to selection of melanoma cells with high levels of glycolysis. Taken together, our findings suggest that molecular targeting of OXPHOS may have efficacy for advanced melanoma.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0040690Titel-ID: cdi_plos_journals_1326266946
- Format
- –
- Schlagworte
- Amino acids, Antineoplastic Agents - pharmacology, Antineoplastic Agents - therapeutic use, Apoptosis, Bioenergetics, Biology, Cancer, Cancer metastasis, Cancer therapies, Cancer treatment, Cell culture, Cell growth, Cell Line, Tumor, Cell Proliferation - drug effects, Cell Respiration - drug effects, Comparative analysis, Dehydrogenases, Development and progression, Drug dosages, Electron transport, Glycolysis, Glycolysis - drug effects, Health aspects, Humans, Hydrazines - pharmacology, Hydrazines - therapeutic use, Hypoxia, Medical prognosis, Medicine, Melanocytes, Melanoma, Melanoma - drug therapy, Melanoma - metabolism, Melanoma - pathology, Metabolism, Metastases, Metastasis, Mitochondria, Mitochondria - drug effects, Mitochondria - metabolism, Mitochondrial Proteins - metabolism, Molecular Targeted Therapy - methods, Oxidative phosphorylation, Oxidative Phosphorylation - drug effects, Oxidative stress, Oxidative Stress - drug effects, Oxygen, Oxygen probes, Pharmacology, Phosphorylation, Proteins, Reactive oxygen species, Reactive Oxygen Species - metabolism, Skin cancer, Stable isotopes, Womens health