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

19 Scopus citations

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

ASJC Scopus subject areas

  • General

Cite this

Saunier, E., Antonio, S., Regazzetti, A., Auzeil, N., Laprévote, O., Shay, J. W., 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, 7(1), [7006]. https://doi.org/10.1038/s41598-017-07006-0