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Mitochondrial respiration - an important therapeutic target in melanoma

Barbi de Moura, M and Vincent, G and Fayewicz, SL and Bateman, NW and Hood, BL and Sun, M and Suhan, J and Duensing, S and Yin, Y and Sander, C and Kirkwood, JM and Becker, D and Conrads, TP and van Houten, B and Moschos, SJ (2012) Mitochondrial respiration - an important therapeutic target in melanoma. PLoS ONE, 7 (8).

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Abstract

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. © 2012 Barbi de Moura et al.

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Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Barbi de Moura, M
Vincent, Ggav10@pitt.eduGAV10
Fayewicz, SL
Bateman, NW
Hood, BL
Sun, Mmas197@pitt.eduMAS197
Suhan, J
Duensing, S
Yin, Y
Sander, Ccas32@pitt.eduCAS32
Kirkwood, JMkirkwood@pitt.eduKIRKWOOD
Becker, D
Conrads, TP
van Houten, Bbev15@pitt.eduBEV15
Moschos, SJ
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorSantos, JanineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 17 August 2012
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 7
Number: 8
DOI or Unique Handle: 10.1371/journal.pone.0040690
Schools and Programs: School of Public Health > Biostatistics
School of Medicine > Pathology
School of Medicine > Pharmacology and Chemical Biology
Refereed: Yes
Other ID: NLM PMC3422349
PubMed Central ID: PMC3422349
PubMed ID: 22912665
Date Deposited: 18 Oct 2012 20:52
Last Modified: 13 Oct 2017 22:58
URI: http://d-scholarship.pitt.edu/id/eprint/15887

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