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.