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

a -Tocopheryl succinate (a -TOS), a redox-inactive analogue of vitamin E, is a strong inducer of apoptosis, whereas -tocopherol (a -TOH) lacks apoptogenic activity (J. Neuzil et al., FASEB J., 15: 403-415, 2001). Here we investigated the possible antineoplastic activities of a -TOH and a -TOS and further explored the potential of -TOS as an antitumor agent. Using nude mice with colon cancer xenografts, we found that a -TOH exerted modest antitumor activity and acted by inhibiting tumor cell proliferation. In contrast, a -TOS showed a more profound antitumor effect, at both the level of inhibition of proliferation and induction of tumor cell apoptosis. a -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, a -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.