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

Clin Cancer Res. 2002 Mar;8(3):863-9.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • CDKN1A protein, human
  • Cdkn1a protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Membrane Glycoproteins
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Tnfsf10 protein, mouse
  • Tumor Necrosis Factor-alpha
  • Tumor Suppressor Protein p53
  • Vitamin E
  • Caspases
  • alpha-Tocopherol
  • Tocopherols