Resveratrol reverses the Warburg effect by targeting the pyruvate dehydrogenase complex in colon cancer cells

Abstract Resveratrol (RES), a polyphenol found in natural foods, displays anti-oxidant, anti-inflammatory and anti-proliferative properties potentially beneficial in cancers, in particular in the prevention of tumor growth. However, the rapid metabolism of resveratrol strongly limits its bioavailabi...

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Autores principales:	Elise Saunier, Samantha Antonio, Anne Regazzetti, Nicolas Auzeil, Olivier Laprévote, Jerry W. Shay, Xavier Coumoul, Robert Barouki, Chantal Benelli, Laurence Huc, Sylvie Bortoli
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3a75a7d127634bdc9062881bbbb61ac9
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spelling	oai:doaj.org-article:3a75a7d127634bdc9062881bbbb61ac92021-12-02T16:08:22ZResveratrol reverses the Warburg effect by targeting the pyruvate dehydrogenase complex in colon cancer cells10.1038/s41598-017-07006-02045-2322https://doaj.org/article/3a75a7d127634bdc9062881bbbb61ac92017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07006-0https://doaj.org/toc/2045-2322Abstract Resveratrol (RES), a polyphenol found in natural foods, displays anti-oxidant, anti-inflammatory and anti-proliferative properties potentially beneficial in cancers, in particular in the prevention of tumor growth. However, the rapid metabolism of resveratrol strongly limits its bioavailability. The molecular mechanisms sustaining the potential biological activity of low doses of resveratrol has not been extensively studied and, thus, needs better characterization. Here, we show that resveratrol (10 µM, 48 hr) induces both a cell growth arrest and a metabolic reprogramming in colon cancer cells. Resveratrol modifies the lipidomic profile, increases oxidative capacities and decreases glycolysis, in association with a decreased pentose phosphate activity and an increased ATP production. Resveratrol targets the pyruvate dehydrogenase (PDH) complex, a key mitochondrial gatekeeper of energy metabolism, leading to an enhanced PDH activity. Calcium chelation, as well as the blockade of the mitochondrial calcium uniport, prevents the resveratrol-induced augmentation in oxidative capacities and the increased PDH activity suggesting that calcium might play a role in the metabolic shift. We further demonstrate that the inhibition of the CamKKB or the downstream AMPK pathway partly abolished the resveratrol-induced increase of glucose oxidation. This suggests that resveratrol might improve the oxidative capacities of cancer cells through the CamKKB/AMPK pathway.Elise SaunierSamantha AntonioAnne RegazzettiNicolas AuzeilOlivier LaprévoteJerry W. ShayXavier CoumoulRobert BaroukiChantal BenelliLaurence HucSylvie BortoliNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-16 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Elise Saunier Samantha Antonio Anne Regazzetti Nicolas Auzeil Olivier Laprévote Jerry W. Shay Xavier Coumoul Robert Barouki Chantal Benelli Laurence Huc Sylvie Bortoli Resveratrol reverses the Warburg effect by targeting the pyruvate dehydrogenase complex in colon cancer cells
description	Abstract Resveratrol (RES), a polyphenol found in natural foods, displays anti-oxidant, anti-inflammatory and anti-proliferative properties potentially beneficial in cancers, in particular in the prevention of tumor growth. However, the rapid metabolism of resveratrol strongly limits its bioavailability. The molecular mechanisms sustaining the potential biological activity of low doses of resveratrol has not been extensively studied and, thus, needs better characterization. Here, we show that resveratrol (10 µM, 48 hr) induces both a cell growth arrest and a metabolic reprogramming in colon cancer cells. Resveratrol modifies the lipidomic profile, increases oxidative capacities and decreases glycolysis, in association with a decreased pentose phosphate activity and an increased ATP production. Resveratrol targets the pyruvate dehydrogenase (PDH) complex, a key mitochondrial gatekeeper of energy metabolism, leading to an enhanced PDH activity. Calcium chelation, as well as the blockade of the mitochondrial calcium uniport, prevents the resveratrol-induced augmentation in oxidative capacities and the increased PDH activity suggesting that calcium might play a role in the metabolic shift. We further demonstrate that the inhibition of the CamKKB or the downstream AMPK pathway partly abolished the resveratrol-induced increase of glucose oxidation. This suggests that resveratrol might improve the oxidative capacities of cancer cells through the CamKKB/AMPK pathway.
format	article
author	Elise Saunier Samantha Antonio Anne Regazzetti Nicolas Auzeil Olivier Laprévote Jerry W. Shay Xavier Coumoul Robert Barouki Chantal Benelli Laurence Huc Sylvie Bortoli
author_facet	Elise Saunier Samantha Antonio Anne Regazzetti Nicolas Auzeil Olivier Laprévote Jerry W. Shay Xavier Coumoul Robert Barouki Chantal Benelli Laurence Huc Sylvie Bortoli
author_sort	Elise Saunier
title	Resveratrol reverses the Warburg effect by targeting the pyruvate dehydrogenase complex in colon cancer cells
title_short	Resveratrol reverses the Warburg effect by targeting the pyruvate dehydrogenase complex in colon cancer cells
title_full	Resveratrol reverses the Warburg effect by targeting the pyruvate dehydrogenase complex in colon cancer cells
title_fullStr	Resveratrol reverses the Warburg effect by targeting the pyruvate dehydrogenase complex in colon cancer cells
title_full_unstemmed	Resveratrol reverses the Warburg effect by targeting the pyruvate dehydrogenase complex in colon cancer cells
title_sort	resveratrol reverses the warburg effect by targeting the pyruvate dehydrogenase complex in colon cancer cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/3a75a7d127634bdc9062881bbbb61ac9
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Resveratrol reverses the Warburg effect by targeting the pyruvate dehydrogenase complex in colon cancer cells

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