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.

Keywords:
Reactive oxygen species, Antitumor drugs, Resveratrol, Uncoupling proteins, Colon cancer
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© 2011 S. Karger AG, Basel
2011
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