Natural tocopherol mixtures as promising cancer preventive agents

Naturally occurring vitamin E, a family of fat-soluble antioxidants, exists in eight chemical forms of α-, β-, γ-, or δ-tocopherols and α-, β-, γ-, or δ-tocotrienols. Tocopherols are the major source of vitamin E in the U.S. diet. Tocopherols are widely occurring in corn, soybean, sesame and cottonseed oils and nuts. Vitamin E is also often consumed as a dietary supplement, with α-tocopherol as the most common form available. Numerous epidemiological studies suggest cancer preventive activity of vitamin E. However, recent large-scale randomized human trials with α-tocopherol did not demonstrate a cancer preventive effect. Importantly, each form of tocopherols has varying levels of biological activity. Our extensive studies in animal models of carcinogenesis have shown the cancer preventive activity of γ-tocopherol and δ-tocopherol as well as a naturally occurring mixture of tocopherols, but the lack of cancer preventive activity by α-tocopherol. Here, we present the anti-cancer activity of natural dietary γ-tocopherol rich tocopherol mixtures, γ-TmT, in two different animal models of estrogen-mediated breast cancer. γ-TmT inhibited estrogen-induced mammary tumorigenesis by lowering the levels of circulating estrogen, increasing estrogen metabolism via regulating metabolizing enzyme, CYP1A1, and facilitating the clearance of toxic metabolites and reactive oxygen species by stimulation of Nrf2-mediated antioxidant response. Activation of PPARγ signaling and inhibition of cell proliferation could also contribute to the chemopreventive effects of γ-TmT. Thus, dietary γ-tocopherol rich mixtures could be safe and effective natural agents for the prevention and treatment of estrogen-induced breast cancer.