Resveratrol in Cancer: Cellular and Mitochondrial Consequences of Proton Transport Inhibition

Guillermo      Lopez-Lluch; Sara      Santa Cruz-Calvo; Placido      Navas

Abstract

Transformed cells suffer several changes leading to the increase of protective mechanisms and show a metabolic profile in accordance with higher proliferative capacity. In these mechanisms, changes in mitochondrial activity cause a higher glycolytic metabolism in detriment of oxidative phosphorylation. In these changes, H+-ATPase regulation seems to be importantly involved. During the last years, polyphenols and specially the stilbene resveratrol and related members of its family have been studied because they are able to affect tumour cell growth and cancer progression. Among the different effects induced by resveratrol, inhibition of H+-ATPase seems to be one important mechanism in its effect on cancer progression. Further, an ectopic H+-ATPase located in the outer surface of plasma membrane has been recently involved in cancer progression and angiogenesis. In this article we review the latest findings about resveratrol inhibition of H+-ATPase and its importance in tumour cell growth and cancer progression.

Keywords: Resveratrol, polyphenols, H+-ATPase, mitochondria, angiogenesis, cell growth, transformed cells, glycolytic metabolism, oxidative phosphorylation, cancer progression