Tocopherols and the treatment of colon cancer.

Colorectal cancer is the second most common cause of cancer deaths in the United States. Vitamin E (VE) and other antioxidants may help prevent colon cancer by decreasing the formation of mutagens arising from the free radical oxidation of fecal lipids or by "non-antioxidant" mechanisms. VE is not a single molecule, but refers to at least eight different molecules, that is, four tocopherols and four tocotrienols. Both animal models and human colon cancer cell lines were used to evaluate the chemopreventive potential of different forms of VE. Rats were fed diets deficient in tocopherols or supplemented with either alpha-tocopherol or gamma-tocopherol. Half the rats in each of these groups received normal levels of dietary Fe and the other half Fe at eight times the normal level. In our cell experiments, we looked at the role of gamma-tocopherol in upregulating peroxisome proliferator-activated receptor-gamma (PPAR-gamma) in the SW 480 human cell line. Rats fed the diets supplemented with alpha-tocopherol had higher levels of VE in feces, colonocytes, plasma, and liver than did rats fed diets supplemented with gamma-tocopherol. Dietary Fe levels did not influence tocopherol levels in plasma, liver, or feces. For colonocytes, high dietary Fe decreased tocopherol levels. Rats fed the gamma-tocopherol-supplemented diets had lower levels of fecal lipid hydroperoxides than rats fed the alpha-tocopherol-supplemented diets. Ras-p21 levels were significantly lower in rats fed the gamma-tocopherol-supplemented diets compared with rats fed the alpha-tocopherol-supplemented diets. High levels of dietary Fe were found to promote oxidative stress in feces and colonocytes. Our data with the SW480 cells suggest that both alpha- and gamma-tocopherol upregulate PPAR-gamma mRNA and protein expression. gamma-tocopherol was, however, found to be a better enhancer of PPAR-gamma expression than alpha-tocopherol at the concentrations tested.