title: Resveratrol induces mitochondrial respiration and apoptosis in SW620 colon cancer cells.
abstract: The polyphenol resveratrol (RSV) is found in the skin of red grapes and has been reported to exhibit anticancer properties. The antitumor effects of RSV in the gastrointestinal tract have gained considerable interest due to the high exposure of this tissue to this dietary compound. One of the hallmarks of cancer cells is their particular metabolism mainly relying on glycolysis for ATP production rather than mitochondrial oxidative phosphorylation. Although RSV has been described to act as a calorie-restriction mimetic, modulating energy metabolism in normal tissues, little efforts have been done to study the effects of this polyphenol in the metabolism of cancer cells. Taking this into account, the aim of this study was to explore metabolic effects of this polyphenol in colon cancer.
  
  
  
  Oxygen consumption, ATP levels, Western blotting and other molecular biology techniques were carried out to characterize the metabolic signature of RSV in SW620 colon cancer cells.
  
  
  
  Paradoxically, the cytotoxic effects of RSV were associated with an increase in oxygen consumption supported by mitochondrial biogenesis and increased fatty acid oxidation. This partial reversion of the Warburg effect was followed by hyperpolarization of mitochondrial membrane and ROS production, leading to an increased apoptosis.
  
  
  
  Our results propose that the anticancer mechanisms of RSV could reside in targeting cancer cell metabolism, promoting mitochondrial electron transport chain overload and, ultimately, increasing ROS production.
  
  
  
  These results shed new light into the anticancer mechanism of RSV supporting the ability of this compound in potentiating the effects of chemotherapy.
authors.affiliation: Grupo Multidisciplinar de Oncología Traslacional, Instituto Universitario de Investigación en Ciencias de la Salud (IUNICS), Palma de Mallorca, Illes Balears, Spain; Ciber Fisiopatología Obesidad y Nutrición (CB06/03), Instituto Salud Carlos III, Madrid, Spain; Instituto de Investigación Sanitaria de Palma (IdISPa), Hospital Universitario Son Espases, edificio S. E-07120, Palma de Mallorca, Illes Balears, Spain.
authors.forename: Mª Del Mar
authors.initials: MD
authors.lastname: Blanquer-Rosselló
authors.affiliation: Grupo Multidisciplinar de Oncología Traslacional, Instituto Universitario de Investigación en Ciencias de la Salud (IUNICS), Palma de Mallorca, Illes Balears, Spain; Ciber Fisiopatología Obesidad y Nutrición (CB06/03), Instituto Salud Carlos III, Madrid, Spain; Instituto de Investigación Sanitaria de Palma (IdISPa), Hospital Universitario Son Espases, edificio S. E-07120, Palma de Mallorca, Illes Balears, Spain.
authors.forename: Reyniel
authors.initials: R
authors.lastname: Hernández-López
authors.affiliation: Grupo Multidisciplinar de Oncología Traslacional, Instituto Universitario de Investigación en Ciencias de la Salud (IUNICS), Palma de Mallorca, Illes Balears, Spain; Ciber Fisiopatología Obesidad y Nutrición (CB06/03), Instituto Salud Carlos III, Madrid, Spain; Instituto de Investigación Sanitaria de Palma (IdISPa), Hospital Universitario Son Espases, edificio S. E-07120, Palma de Mallorca, Illes Balears, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Roca
authors.affiliation: Grupo Multidisciplinar de Oncología Traslacional, Instituto Universitario de Investigación en Ciencias de la Salud (IUNICS), Palma de Mallorca, Illes Balears, Spain; Ciber Fisiopatología Obesidad y Nutrición (CB06/03), Instituto Salud Carlos III, Madrid, Spain; Instituto de Investigación Sanitaria de Palma (IdISPa), Hospital Universitario Son Espases, edificio S. E-07120, Palma de Mallorca, Illes Balears, Spain. Electronic address: jordi.oliver@uib.es.
authors.forename: Jordi
authors.initials: J
authors.lastname: Oliver
authors.affiliation: Grupo Multidisciplinar de Oncología Traslacional, Instituto Universitario de Investigación en Ciencias de la Salud (IUNICS), Palma de Mallorca, Illes Balears, Spain; Ciber Fisiopatología Obesidad y Nutrición (CB06/03), Instituto Salud Carlos III, Madrid, Spain; Instituto de Investigación Sanitaria de Palma (IdISPa), Hospital Universitario Son Espases, edificio S. E-07120, Palma de Mallorca, Illes Balears, Spain.
authors.forename: Adamo
authors.initials: A
authors.lastname: Valle
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D031204:Caloric Restriction / Q000379:methods; D045744:Cell Line, Tumor; D019069:Cell Respiration / Q000187:drug effects*; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D005227:Fatty Acids; D017382:Reactive Oxygen Species; D013267:Stilbenes; D000255:Adenosine Triphosphate; D000077185:Resveratrol
keywords: Apoptosis; Colon cancer; Metabolism; Mitochondria; Resveratrol; SW620