Vitamin E succinate is a potent novel antineoplastic agent with high selectivity and cooperativity with tumor necrosis factor-related apoptosis-inducing ligand (Apo2 Ligand) in vivo

Abstract

α -Tocopheryl succinate (α -TOS), a redox-inactive analogue of vitamin E, is a strong inducer of apoptosis, whereas -tocopherol (α -TOH) lacks apoptogenic activity (J. Neuzil et al., FASEB J., 15: 403–415, 2001). Here we investigated the possible antineoplastic activities of α -TOH and α -TOS and further explored the potential of -TOS as an antitumor agent. Using nude mice with colon cancer xenografts, we found that α -TOH exerted modest antitumor activity and acted by inhibiting tumor cell proliferation. In contrast, α -TOS showed a more profound antitumor effect, at both the level of inhibition of proliferation and induction of tumor cell apoptosis. α -TOS was nontoxic to normal cells and tissues, triggered apoptosis in p53-/- and p21Waf1/Cip1(-/-) cancer cells, and exerted a cooperative proapoptotic activity with tumor necrosis factor-related apoptosis-inducing ligand (Apo2 ligand) due to differences in proapoptotic signaling. Finally, α -TOS cooperated with tumor necrosis factor-related apoptosis-inducing ligand in suppression of tumor growth in vivo. Vitamin E succinate is thus a potent and highly specific anticancer agent and/or adjuvant of considerable therapeutic potential.