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