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.

Weber T, Lu M, Andera L, Lahm H, Gellert N, Fariss MW, Korinek V, Sattler W, Ucker DS, Terman A, Schröder A, Erl W, Brunk UT, Coffey RJ, Weber C, Neuzil J
Clin Cancer Res. 2002 8 (3): 863-9

PMID: 11895920

Alpha-tocopheryl succinate (alpha-TOS), a redox-inactive analogue of vitamin E, is a strong inducer of apoptosis, whereas alpha-tocopherol (alpha-TOH) lacks apoptogenic activity (J. Neuzil et al., FASEB J., 15: 403-415, 2001). Here we investigated the possible antineoplastic activities of alpha-TOH and alpha-TOS and further explored the potential of alpha-TOS as an antitumor agent. Using nude mice with colon cancer xenografts, we found that alpha-TOH exerted modest antitumor activity and acted by inhibiting tumor cell proliferation. In contrast, alpha-TOS showed a more profound antitumor effect, at both the level of inhibition of proliferation and induction of tumor cell apoptosis. alpha-TOS was nontoxic to normal cells and tissues, triggered apoptosis in p53(-/-) and p21(Waf1/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, alpha-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.

MeSH Terms (25)

alpha-Tocopherol Animals Antineoplastic Agents Apoptosis Apoptosis Regulatory Proteins Caspases Colonic Neoplasms Colony-Forming Units Assay Cyclin-Dependent Kinase Inhibitor p21 Cyclins Drug Synergism Humans Membrane Glycoproteins Mice Myocardial Contraction Myocardium Neoplasm Invasiveness TNF-Related Apoptosis-Inducing Ligand Tocopherols Transfection Tumor Cells, Cultured Tumor Necrosis Factor-alpha Tumor Suppressor Protein p53 Vitamin E Xenograft Model Antitumor Assays

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