The dietary antioxidants resveratrol and quercetin protect cells from exogenous pro-oxidative damage.

In the colorectal epithelium oxidative stress is observed endogenously in premalignant adenoma cells or induced by nutritional factors like fatty acid hydroperoxides (LOOH). Bioactive phenols like resveratrol and quercetin can quench reactive oxygen species and protect from pro-oxidative damage. Our study used colorectal adenoma and carcinoma cell lines to assess antioxidant protective effects of resveratrol and quercetin. It demonstrated that both compounds efficiently protect from oxidative stress induced by LOOH. Effective concentrations (10 microM resveratrol and 1 microM quercetin) can easily be reached in the intestinal lumen after consumption of plant foods or food supplements. Both compounds prevent LOOH-induced formation of intracellular H2O2, stimulation of cyclooxygenase-2 and vascular endothelial growth factor. For reduction of endogenous H2O2 levels in colorectal tumor cells higher antioxidant-concentrations are needed in all cell lines. Quercetin (10 microM) alone even increased H2O2 in LT97 adenoma cells and stimulated VEGF production. Resveratrol and quercetin also induced 10-30% and 40-60% cell loss respectively by apoptosis. In summary, this indicates that resveratrol and quercetin have little protective capacity in absence of exogenous stress. They are however highly efficient in protecting against nutrition induced oxidative stress damage suggesting that this constitutes the major part of their tumor protective activity.

Suppression of tumour-promoting factors in fat-induced colon carcinogenesis by the antioxidants caroverine and ubiquinone.

Fatty acid hydroperoxides are produced from unsaturated fatty acids in the presence of oxygen at elevated temperatures during food processing. Their effects on gene expression in colorectal tumour cells were studied using linoleic acid hydroperoxide (LOOH) as a model compound. Addition of LOOH to the medium of LT97 adenoma and SW480 carcinoma cells enhanced the production of hydrogen peroxide. Both cell lines were observed to increase VEGF factors based on mRNA. High consumption of dietary fat promotes colon carcinogenesis in the long-term. While this effect is well known, the underlying mechanisms are not understood. An approach was made starting from the assumption that LOOH is present in dietary fats as a result of heating. LOOH undergoes homolytic cleavage in the presence of iron. Various radicals are formed on mixing LT97 or SW480 cells with LOOH. The expression of tumour-promoting factors was inhibited by caroverine and ubiquinone, which may be justified as active chemopreventive agents.

Ubiquinol and the papaverine derivative caroverine prevent the expression of tumour- promoting factors in adenoma and carcinoma colon cancer cells induced by dietary fat.

High consumption of dietary fat promotes colon carcinogenesis. While this effect is well known the underlying mechanism is not understood. Fatty acid hydroperoxides (LOOH) arise from unsaturated fatty acids in the presence of oxygen and elevated temperature during food processing. An approach was made starting from the assumption that LOOH are present in dietary fats as a result of boiling. LOOH undergoes homolytic cleavage in the presence of iron. We studied their effects on gene expression in colorectal tumour cells using linoleic acid hydroperoxide (LOOH) as model compound. Addition to the medium of LT97 adenoma and SW480 carcinoma cells enhanced the production of hydrogen peroxide. Both cell lines were observed to increase VEGF and COX-II expression based on mRNA. Expression of VEGF was inhibited by caroverine and ubiquinon.