Cancer Prevention by Different Forms of Tocopherols

CHUNG S. YANG*, GUANGXUN LI AND ZHIHONG YANG

Department of Chemical Biology, Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, U.S.A.

ABSTRACT

Low vitamin E nutritional status has been suggested to increase cancer risk. However, recent large-scale human trials with high doses of alpha-tocopherol (-T) have produced disappointing results. This points out the need for a better understanding of the biological activities of different forms of tocopherols. Using a tocopherol mixture that is rich in -T (-TmT), we demonstrated the inhibition of colon carcinogenesis in mice, and the inhibition is associated with decreased levels of 8-isoprostane, nitrotyrosine, prostaglandin E2 and leukotriene B4. Dietary 0.3% -TmT also inhibited chemically induced lung tumorigenesis in the A/J mice as well as the growth of lung cancer cells in xenograft or allograft tumors; the inhibition was associated with a reduction of oxidative/nitrosative stress. -T was found to be more active than -T in the inhibition of cancer cell growth in culture and lung cancer xenograft tumors as well as in azoxymethane-induced colon aberrant crypt foci formation in rats, whereas -T was ineffective. Analysis of the levels of tocopherols and their metabolites in blood and tissues suggests that metabolites of -T and -T contribute to their inhibitory activity. These studies demonstrate the broad cancer preventive activity of -TmT and higher activity of -T.

Key words: tocopherols, vitamin E, inhibition, colon cancer, lung cancer