Abstract 5235: Dietary administration of δ- and γ-tocopherol inhibits estrogen-mediated mammary tumorigenesis in ACI rats

Abstract

Abstract Tocopherols (T), members of the vitamin E family, occur in four forms designated as α, β, δ and γ. Epidemiological studies suggest that tocopherols could reduce the risk of cancer. α-T is known as the classical vitamin E, being the predominant form of tocopherol found in human blood and tissues. However, clinical studies with α-T to substantiate the role of tocopherols in cancer prevention have provided inconclusive results. Such outcomes indicate that the cancer preventive activity of tocopherols might be attributed to the other forms of tocopherols, but not α-T. γ-T, which is the most abundant tocopherol in vegetable oils, is our major dietary source of tocopherols. Recent studies have demonstrated that δ-T and γ-T have higher anti-cancer activity than α-T in several animal models of cancer. The present study investigated the cancer preventive activity of individual purified forms of tocopherols α-T, δ-T, γ-T as well as a naturally occurring γ-T rich mixture of tocopherols (γ-TmT) in an in vivo model of estrogen receptor (ER)-positive breast cancer, namely estrogen supplemented August-Copenhagen Irish (ACI) rats. ACI rats were subcutaneously implanted with 9 mg of 17β-estradiol (E2) in silastic tubings and administered with diets containing 0.2% α-T, δ-T, γ-T or γ-TmT. Rats were euthanized at 30 weeks of mammary carcinogenesis when the E2 control group exhibited 100% tumor incidence. α-T had no effect on estrogen-induced mammary tumors. However, treatment with 0.2% δ-T, γ-T and γ-TmT reduced the tumor volume by 51% (p<0.05), 60% (p<0.01) and 59% (p<0.01), respectively. Administration of α-T, δ-T and γ-T resulted in a 2.1-, 80- and 62-fold increase of these tocopherols, respectively, in the serum of ACI rats. Supplementation with the individual tocopherols also increased the levels of their respective short chain metabolite, carboxyethyl hydroxychromans (CEHCs) in the serum. Administration of δ-T and γ-T was associated with 185- and 99-fold increase in their CEHC metabolites, respectively. The high serum levels of δ- and γ-CEHC metabolites could contribute to the enhanced chemopreventive activity of δ-T and γ-T. In conclusion, δ-T, γ-T and γ-TmT could be potential natural agents for the prevention of estrogen-induced mammary tumorigenesis. (This work was supported by the NIH grant R01 AT007036 and the New Jersey Commission on Cancer Research Postdoctoral Fellowship to Soumyasri Das Gupta). Citation Format: Soumyasri Das Gupta, Joseph Wahler, Min Ji Bak, Mao-Jung Lee, Yong Lin, Weichung Joe Shih, Chung S Yang, Nanjoo Suh. Dietary administration of δ- and γ-tocopherol inhibits estrogen-mediated mammary tumorigenesis in ACI rats. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5235.