Resveratrol Potentiates the Cytotoxic Oxidative Stress Induced by Chemotherapy in Human Colon Cancer Cells

Cellular Physiology and Biochemistry

关键词: Reactive oxygen species;    Antitumor drugs;    Resveratrol;    Uncoupling proteins;    Colon cancer;   

DOI  :  10.1159/000331733

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

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.

【 授权许可】

CC BY-NC-ND