期刊
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
卷 28, 期 2, 页码 219-228出版社
KARGER
DOI: 10.1159/000331733
关键词
Reactive oxygen species; Antitumor drugs; Resveratrol; Uncoupling proteins; Colon cancer
资金
- Spanish Government [PI060266, PS09/01637]
- Conselleria d'Economia, Hisenda i Innovacio del Govern de les Illes Balears
- Fundacion Cientifica de la Asociacion Espanola Contra el Cancer (AECC)
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. Copyright (C) 2011 S. Karger AG, Basel
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