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Int. J. Mol. Sci. 2017, 18(8), 1620; doi:10.3390/ijms18081620

Melatonin Decreases Glucose Metabolism in Prostate Cancer Cells: A 13C Stable Isotope-Resolved Metabolomic Study

1
Departamento de Morfologia y Biologia Celular, Instituto Universitario Oncologico del Principado de Asturias (IUOPA), Universidad de Oviedo, 33006 Oviedo, Spain
2
Departamento de Quimica Fisica y Analitica, Universidad de Oviedo, 33006 Oviedo, Spain
3
Servicios Cientifico Tecnicos, Edificio Severo Ochoa, Universidad de Oviedo, 33006 Oviedo, Spain
*
Authors to whom correspondence should be addressed.
Received: 2 July 2017 / Revised: 18 July 2017 / Accepted: 20 July 2017 / Published: 26 July 2017
(This article belongs to the Special Issue Melatonin and Its Analogues: Experimental and Clinical Aspects)
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Abstract

The pineal neuroindole melatonin exerts an exceptional variety of systemic functions. Some of them are exerted through its specific membrane receptors type 1 and type 2 (MT1 and MT2) while others are mediated by receptor-independent mechanisms. A potential transport of melatonin through facilitative glucose transporters (GLUT/SLC2A) was proposed in prostate cancer cells. The prostate cells have a particular metabolism that changes during tumor progression. During the first steps of carcinogenesis, oxidative phosphorylation is reactivated while the switch to the “Warburg effect” only occurs in advanced tumors and in the metastatic stage. Here, we investigated whether melatonin might change prostate cancer cell metabolism. To do so, 13C stable isotope-resolved metabolomics in androgen sensitive LNCaP and insensitive PC-3 prostate cancer cells were employed. In addition to metabolite 13C-labeling, ATP/AMP levels, and lactate dehydrogenase or pentose phosphate pathway activity were measured. Melatonin reduces lactate labeling in androgen-sensitive cells and it also lowers 13C-labeling of tricarboxylic acid cycle metabolites and ATP production. In addition, melatonin reduces lactate 13C-labeling in androgen insensitive prostate cancer cells. Results demonstrated that melatonin limits glycolysis as well as the tricarboxylic acid cycle and pentose phosphate pathway in prostate cancer cells, suggesting that the reduction of glucose uptake is a major target of the indole in this tumor type. View Full-Text
Keywords: melatonin; metabolism; 13C-glucose; lactate; ATP; prostate cancer melatonin; metabolism; 13C-glucose; lactate; ATP; prostate cancer
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Hevia, D.; Gonzalez-Menendez, P.; Fernandez-Fernandez, M.; Cueto, S.; Rodriguez-Gonzalez, P.; Garcia-Alonso, J.I.; Mayo, J.C.; Sainz, R.M. Melatonin Decreases Glucose Metabolism in Prostate Cancer Cells: A 13C Stable Isotope-Resolved Metabolomic Study. Int. J. Mol. Sci. 2017, 18, 1620.

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