Anticancer actions of natural and synthetic vitamin E forms: RRR-alpha-tocopherol blocks the anticancer actions of gamma-tocopherol

Two naturally occurring dietary sources of vitamin E (i.e. RRR-alpha-tocopherol (alpha T) and RRR-gamma-tocopherol (gamma T)), the manufactured synthetic form of vitamin E, all-racemic-alpha-tocopherol (all-rac-alpha T), as well as a potent antitumor analog of vitamin E, RRR-alpha-tocopherol ether-linked acetic acid analog (alpha-TEA), were assessed for anticancer actions. Data showed that gamma T, all-rac-alpha T, and alpha-TEA but not alpha T or alpha T+gamma T significantly inhibited tumor burden of human MDA-MB-231 cells in nude mice. Immunohistochemical analyses of tumor tissue showed that all-rac-alpha T and alpha-TEA increased apoptosis and decreased proliferation in tumor cells while gamma T was associated with increased tumor cell apoptosis only. In vitro data showed alpha-TEA and gamma T but not all-rac-alpha T or alpha T to inhibit colony formation and induce apoptosis. Anticancer actions of alpha-TEA and gamma T involved death receptor 5 protein upregulation, Survivin protein downregulation and poly (ADP-ribose) polymerase cleavage, all of which were blocked by co-treatment with alpha T. In summary, both gamma T and alpha-TEA exhibited promising anticancer properties in vivo and in vitro, whereas all-rac-alpha T exhibited promising anticancer properties in vivo only. Importantly, alpha T not only failed to exhibit anticancer properties but it also reduced anticancer actions of gamma T in vivo and gamma T and alpha-TEA in vitro.