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Melatonin Cytotoxicity Is Associated to Warburg Effect Inhibition in Ewing Sarcoma Cells
Melatonin kills or inhibits the proliferation of different cancer cell types, and this is associated with an increase or a decrease in reactive oxygen species, respectively. Intracellular oxidants originate mainly from oxidative metabolism, and cancer cells frequently show alterations in this metabo...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4529102/ https://www.ncbi.nlm.nih.gov/pubmed/26252771 http://dx.doi.org/10.1371/journal.pone.0135420 |
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author | Sanchez-Sanchez, Ana M. Antolin, Isaac Puente-Moncada, Noelia Suarez, Santos Gomez-Lobo, Marina Rodriguez, Carmen Martin, Vanesa |
author_facet | Sanchez-Sanchez, Ana M. Antolin, Isaac Puente-Moncada, Noelia Suarez, Santos Gomez-Lobo, Marina Rodriguez, Carmen Martin, Vanesa |
author_sort | Sanchez-Sanchez, Ana M. |
collection | PubMed |
description | Melatonin kills or inhibits the proliferation of different cancer cell types, and this is associated with an increase or a decrease in reactive oxygen species, respectively. Intracellular oxidants originate mainly from oxidative metabolism, and cancer cells frequently show alterations in this metabolic pathway, such as the Warburg effect (aerobic glycolysis). Thus, we hypothesized that melatonin could also regulate differentially oxidative metabolism in cells where it is cytotoxic (Ewing sarcoma cells) and in cells where it inhibits proliferation (chondrosarcoma cells). Ewing sarcoma cells but not chondrosarcoma cells showed a metabolic profile consistent with aerobic glycolysis, i.e. increased glucose uptake, LDH activity, lactate production and HIF-1α activation. Melatonin reversed Ewing sarcoma metabolic profile and this effect was associated with its cytotoxicity. The differential regulation of metabolism by melatonin could explain why the hormone is harmless for a wide spectrum of normal and only a few tumoral cells, while it kills specific tumor cell types. |
format | Online Article Text |
id | pubmed-4529102 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-45291022015-08-12 Melatonin Cytotoxicity Is Associated to Warburg Effect Inhibition in Ewing Sarcoma Cells Sanchez-Sanchez, Ana M. Antolin, Isaac Puente-Moncada, Noelia Suarez, Santos Gomez-Lobo, Marina Rodriguez, Carmen Martin, Vanesa PLoS One Research Article Melatonin kills or inhibits the proliferation of different cancer cell types, and this is associated with an increase or a decrease in reactive oxygen species, respectively. Intracellular oxidants originate mainly from oxidative metabolism, and cancer cells frequently show alterations in this metabolic pathway, such as the Warburg effect (aerobic glycolysis). Thus, we hypothesized that melatonin could also regulate differentially oxidative metabolism in cells where it is cytotoxic (Ewing sarcoma cells) and in cells where it inhibits proliferation (chondrosarcoma cells). Ewing sarcoma cells but not chondrosarcoma cells showed a metabolic profile consistent with aerobic glycolysis, i.e. increased glucose uptake, LDH activity, lactate production and HIF-1α activation. Melatonin reversed Ewing sarcoma metabolic profile and this effect was associated with its cytotoxicity. The differential regulation of metabolism by melatonin could explain why the hormone is harmless for a wide spectrum of normal and only a few tumoral cells, while it kills specific tumor cell types. Public Library of Science 2015-08-07 /pmc/articles/PMC4529102/ /pubmed/26252771 http://dx.doi.org/10.1371/journal.pone.0135420 Text en © 2015 Sanchez-Sanchez et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Sanchez-Sanchez, Ana M. Antolin, Isaac Puente-Moncada, Noelia Suarez, Santos Gomez-Lobo, Marina Rodriguez, Carmen Martin, Vanesa Melatonin Cytotoxicity Is Associated to Warburg Effect Inhibition in Ewing Sarcoma Cells |
title | Melatonin Cytotoxicity Is Associated to Warburg Effect Inhibition in Ewing Sarcoma Cells |
title_full | Melatonin Cytotoxicity Is Associated to Warburg Effect Inhibition in Ewing Sarcoma Cells |
title_fullStr | Melatonin Cytotoxicity Is Associated to Warburg Effect Inhibition in Ewing Sarcoma Cells |
title_full_unstemmed | Melatonin Cytotoxicity Is Associated to Warburg Effect Inhibition in Ewing Sarcoma Cells |
title_short | Melatonin Cytotoxicity Is Associated to Warburg Effect Inhibition in Ewing Sarcoma Cells |
title_sort | melatonin cytotoxicity is associated to warburg effect inhibition in ewing sarcoma cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4529102/ https://www.ncbi.nlm.nih.gov/pubmed/26252771 http://dx.doi.org/10.1371/journal.pone.0135420 |
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