Short Communication

British Journal of Cancer (2001) 84, 87–89. doi:10.1054/bjoc.2000.1559 www.bjcancer.com
Published online 3 January 2001

Selective cancer cell killing by alpha-tocopheryl succinate

J Neuzil1, T Weber1, N Gellert1 and C Weber1

1Institute for Prevention of Cardiovascular Diseases, Ludwig Maximilians University, Pettenkoferstrasse 9, Munich, 80336, Germany

Correspondence: J Neuzil, E-mail: jneuzil@klp.med.uni-muenchen.de; C Weber, E-mail: cweber@klp.med.uni-muenchen.de

Received 6 June 2000; Revised 8 September 2000; Accepted 18 September 2000.

Top

Abstract

We report that alpha-tocopheryl succinate, a vitamin E analogue with pro-apoptotic properties, selectively kills cells with a malignant or transformed phenotype, i.e. multiple haematopoietic and carcinoma cell lines, while being non-toxic to normal, i.e. primary and non-transformed cells. These findings strongly suggest a potential of this micronutrient in the therapy and/or prevention of cancer without significant side-effects. © 2001 Cancer Research Campaign

Keywords:

vitamin E analogue, malignant cells, apoptosis, selectivity

Top

References

  1. Bendich A and Machlin LJ (1988) Safety of oral intake of vitamin E. Am J Clin Nutr 48: 612–619 | PubMed | ISI | ChemPort |
  2. Chinery R, Brockman JA, Peeler Mo, Shyr Y, Beauchamp RD and Coffey RJ (1997) Antioxidants enhance the toxicity of chemotherapeutic agents in colorectal cancer: A p53-independent induction of p21Waf1/Cip1via C/EBP beta. Nature Med 3: 1233–1241 | Article |
  3. Engers R, Mrzyk S, Springer E, Fabbro D, Weissgerber G, Gernharz CD and Gabbert HE (2000) Protein kinase C in human renal cell carcinomas: role in invasion and differential isoenzyme expression. Br J Cancer 82: 1063–1069 | Article |
  4. Fariss MW, Fortuna MB, Everett CK, Smith JD, Trent DF and Djuric Z (1994) The selective antiproliferative effects of alpha-tocopheryl hemisuccinate and cholesteryl hemisuccinate on murine leukemia cells result from the action of the intact compounds. Cancer Res 54: 3346–3351 | PubMed | ISI | ChemPort |
  5. Frey MR, Saxon ML, Zho X, Rollins A, Evans SS and Black JD (1997) Protein kinase C isozyme-mediated cell cycle arrest involves induction of p21Waf1/Cip1and p27Kip1and hypophosphorylation of the retinoblastoma protein in intestinal epithelial cells. J Biol Chem 272: 9424–9435 | Article | PubMed | ISI | ChemPort |
  6. Henderson IC and Frei E (1980) Adriamycin cardiotoxicity. Am Heart J 99: 671–674
  7. Israel K, Yu W, Sanders BG and Kline K (2000) Vitamin E succinate induces apoptosis in human prostate cancer cells: role for Fas in vitamin E succinate-triggered apoptosis. Nutr Cancer 36: 90–100 | Article | PubMed | ISI | ChemPort |
  8. Jha MN, Bedford JS, Cole WC, Edward-Prasad J and Prasad KN (1999) Vitamin E (d-alpha-tocopheryl succinate) decreases mitotic accumulation in gamma-irradiated human tumor, but not in normal cells. Nutr Cancer 35: 189–194
  9. Jo M, Kim TH, Seol DW, Esplen JE, Dorko K, Billiar TR and Strom SC (2000) Apoptosis induced in normal human hepatocytes by tumor necrosis factor-related apoptosis-inducing ligand. Nature Med 6: 564–567
  10. Kaelin WG (1999) Choosing anticancer drug targets in the postgenomic era. J Clin Invest 104: 1645–1506
  11. Neuzil J, Svensson I, Weber T, Weber C and Brunk U (1999) alpha-Tocopheryl succinate-induced apoptosis in Jurkat T cells involves caspase-3 activation, and both lysosomal and mitochondrial destabilisation. FEBS Lett 445: 295–300 | Article | PubMed | ISI | ChemPort |
  12. Neuzil J, Weber T, Schroeder A, Lu M, Ostermann G, Gellert N, Mayne GC, Olejnicka B, Negre-Salvayre A, Sticha M, Coffey RJ and Weber C (2001) Induction of cancer cell apoptosis by alpha-tocopheryl succinate: molecular pathways and structural requirements. FASEB J,
  13. Qian M, Kralova J, Yu W, Bose HR, Dvorak M, Sanders BG and Kline K (1997) c-Jun involvement in vitamin E succinate induced apoptosis of reticuloendotheliosis virus transformed avian lymphoid cells. Oncogene 15: 223–230 | Article | PubMed | ISI | ChemPort |
  14. Turley JM, Ruscetti FW, Kim SJ, Fu T, Gou FV and Birchenall-Roberts MC (1997) Vitamin E succinate inhibits proliferation of BT-20 human breast cancer cells: increased binding of cyclin A negatively regulates E2F transactivation activity. Cancer Res 57: 2668–2675 | ISI | ChemPort |
  15. Ways DK, Kukoly CA, deVente J, Hooker JL, Bryant WO, Posekany KJ, Fletscher DJ, Cook PP and Parker PJ (1995) MCF-7 breast cancer cells transfected with protein kinase C-alpha exhibit altered expression of other protein kinase C isoforms and display a more aggressive neoplastic phenotype. J Clin Invest 95: 1906–1915 | PubMed | ISI | ChemPort |