title: Resveratrol potentiates the cytotoxic oxidative stress induced by chemotherapy in human colon cancer cells.
abstract: The treatment of advanced colorectal cancer with 5-fluorouracil has two major problems: development of tumor resistance and toxicity toward normal tissues. The aim of this study was to investigate the possible advantages of combining 5-fluorouracil (5-FU) with resveratrol (trans-3, 4', 5-trihydroxystilbene) for treating HT-29 and SW-620 colorectal carcinoma cell lines. Since combined treatment using 5-FU with resveratrol resulted in a significant decrease in long-term cell survival, we investigated the possible basis of this synergistic interaction at a molecular level, focusing on oxidative stress as a possible mediator of cell death. Resveratrol established interactions with the mitochondria of cancer cells and induced an imbalance in cellular antioxidant activities, leading to a significant increase in the levels of both intracellular reactive oxygen species (ROS) and lipid peroxides. Combined treatment with resveratrol sensitized colon cancer cells to 5-fluorouracil, inducing a further increase in oxidative stress, which was linked to the inhibition of AKT and STAT3 proteins, which are known to have oncogenic potential in colorectal carcinomas.
authors.affiliation: Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS). Universitat de les Illes Balears, Palma de Mallorca, Illes Balears, Spain.
authors.forename: Francisca M
authors.initials: FM
authors.lastname: Santandreu
authors.forename: Adamo
authors.initials: A
authors.lastname: Valle
authors.forename: Jordi
authors.initials: J
authors.lastname: Oliver
authors.forename: Pilar
authors.initials: P
authors.lastname: Roca
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism / Q000503:physiopathology; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor; D013267:Stilbenes; D051057:Proto-Oncogene Proteins c-akt; D000077185:Resveratrol; D005472:Fluorouracil