Cancer prevention by different forms of tocopherols.

Many epidemiological studies have suggested that a low vitamin E nutritional status is associated with increased cancer risk. However, several recent large-scale human trials with high doses of α-tocopherol (α-T) have produced disappointing results. This points out the need for a better understanding of the biological activities of the different forms of tocopherols. Using a naturally occurring tocopherol mixture (γ-TmT) that is rich in γ-T, we demonstrated the inhibition of chemically induced lung, colon, and mammary cancer formation as well as the growth of xenograft tumors derived from human lung and prostate cancer cells. This broad anticancer activity of γ-TmT has been attributed mainly to the trapping of reactive oxygen and nitrogen species and inhibition of arachidonic acid metabolism. Activation of peroxisome proliferator-activated receptor γ (PPARγ) and the inhibition of estrogen signaling have also been observed in the inhibition of mammary cancer development. δ-T has been shown to be more active than γ-T in inhibiting the growth of human lung cancer cells in a xenograft tumor model and the development of aberrant crypt foci in azoxymethane-treated rats, whereas α-T is not effective in these models. The higher inhibitory activities of δ-T and γ-T (than α-T) are proposed to be due to their trapping of reactive nitrogen species and their capacity to generate side-chain degradation products, which retain the intact chromanol ring structure and could have cancer preventive activities.