Vitamin E Isoforms: Multiple Mechanisms of Action Against Carcinogenesis

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Cancer is the second leading cause of death in the United States and is expected to become the primary cause of disease-related death within the next decade. There are significant country-to-country variations in cancer incidence, which suggests that nutrition and dietary factors are important to the carcinogenesis process. An increased risk of cancer is associated with obesity and a high body mass index demonstrating that nutrition has a central role in the promotion of cancer. Healthy eating habits protect against cancer, while unhealthy eating habits increase the risk of cancer. Mediterranean societies have a lower risk for many cancers than those of northern Europe and the Americas. Mediterranean diets consist of a high consumption of fruits, vegetables, grains, beans, nuts, and seeds, with olive oil as an important source of monounsaturated fat. These foods are rich in lipid soluble antioxidants such as vitamin E. Vitamin E may prevent cancer by decreasing the formation of mutagens arising from the oxidation of lipids, decreasing oxidative stress in the epithelial cells as well as modulating molecular mechanisms that influence cell death, cell cycle, and transcriptional events. Vitamin E is a major fat-soluble antioxidant and it occurs naturally as eight compounds (alpha-, beta gamma-, and delta-tocopherol or alpha-, beta-, gamma-, and delta-tocotrienol). Since the recognition of vitamin E in 1922 as an essential nutrient for reproduction, alphatocopherol has been considered the major form of vitamin E. It has the highest concentration in the plasma and has been studied more in epidemiological and clinical studies than any other form of vitamin E. Recent data suggests that other isoforms of vitamin E may be important in the control of cancer. These isoforms of vitamin E have varying anti-carcinogenic potencies. Data indicate that gamma-tocopherol may be a more effective anti-cancer agent than alpha-tocopherol. Our laboratories and others have demonstrated that tocotrienols are even more effective than tocopherols at inhibiting cell proliferation in cancer cells. Differences in apoptotic induction among the various vitamin E isoforms are reflective of different avenues of apoptotic signaling and may be tissue specific. Dietary fat has been linked to an increase in a number of cancers including colon, prostate, and breast cancer. Vitamin E modulates a number of molecular mechanisms involved in fat metabolism. These include: the peroxisome proliferator activator receptor (PPAR), arachidonic acid metabolism, de novo sphingolipid metabolism, and cholesterol metabolism. Vitamin E family members have demonstrated the potential to activate pathways involved in cell proliferation, differentiation, apoptosis, and cell cycle. This chapter reviews data that identify the molecular targets of vitamin E action against the development of cancer.

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