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

Elise Saunier, Samantha Antonio, Anne Regazzetti, Nicolas Auzeil, Olivier Laprévote, Jerry W. Shay, Xavier Coumoul, Robert Barouki, Chantal Benelli, Laurence Huc, Sylvie Bortoli

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish (US)
Article number7006
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

Fingerprint

Pyruvate Dehydrogenase Complex
Colonic Neoplasms
AMP-Activated Protein Kinases
Calcium
Pyruvic Acid
Oxidoreductases
Pentoses
resveratrol
Neoplasms
Ion Transport
Polyphenols
Glycolysis
Growth
Oxidants
Energy Metabolism
Biological Availability
Anti-Inflammatory Agents
Adenosine Triphosphate
Phosphates
Glucose

ASJC Scopus subject areas

  • General

Cite this

Resveratrol reverses the Warburg effect by targeting the pyruvate dehydrogenase complex in colon cancer cells. / Saunier, Elise; Antonio, Samantha; Regazzetti, Anne; Auzeil, Nicolas; Laprévote, Olivier; Shay, Jerry W.; Coumoul, Xavier; Barouki, Robert; Benelli, Chantal; Huc, Laurence; Bortoli, Sylvie.

In: Scientific Reports, Vol. 7, No. 1, 7006, 01.12.2017.

Research output: Contribution to journalArticle

Saunier, E, Antonio, S, Regazzetti, A, Auzeil, N, Laprévote, O, Shay, JW, Coumoul, X, Barouki, R, Benelli, C, Huc, L & Bortoli, S 2017, 'Resveratrol reverses the Warburg effect by targeting the pyruvate dehydrogenase complex in colon cancer cells', Scientific Reports, vol. 7, no. 1, 7006. https://doi.org/10.1038/s41598-017-07006-0
Saunier, Elise ; Antonio, Samantha ; Regazzetti, Anne ; Auzeil, Nicolas ; Laprévote, Olivier ; Shay, Jerry W. ; Coumoul, Xavier ; Barouki, Robert ; Benelli, Chantal ; Huc, Laurence ; Bortoli, Sylvie. / Resveratrol reverses the Warburg effect by targeting the pyruvate dehydrogenase complex in colon cancer cells. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
@article{3326bd06197d4f0d8198432a6ce4ffa4,
title = "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 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.",
author = "Elise Saunier and Samantha Antonio and Anne Regazzetti and Nicolas Auzeil and Olivier Lapr{\'e}vote and Shay, {Jerry W.} and Xavier Coumoul and Robert Barouki and Chantal Benelli and Laurence Huc and Sylvie Bortoli",
year = "2017",
month = "12",
day = "1",
doi = "10.1038/s41598-017-07006-0",
language = "English (US)",
volume = "7",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Resveratrol reverses the Warburg effect by targeting the pyruvate dehydrogenase complex in colon cancer cells

AU - Saunier, Elise

AU - Antonio, Samantha

AU - Regazzetti, Anne

AU - Auzeil, Nicolas

AU - Laprévote, Olivier

AU - Shay, Jerry W.

AU - Coumoul, Xavier

AU - Barouki, Robert

AU - Benelli, Chantal

AU - Huc, Laurence

AU - Bortoli, Sylvie

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85026672986&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85026672986&partnerID=8YFLogxK

U2 - 10.1038/s41598-017-07006-0

DO - 10.1038/s41598-017-07006-0

M3 - Article

VL - 7

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 7006

ER -