Vitamin E succinate suppresses prostate tumor growth by inducing apoptosis

Int J Cancer. 2006 May 15;118(10):2441-7. doi: 10.1002/ijc.21689.

Abstract

Prostate cancer is a major cause of cancer death and morbidity in western countries. However, because of its intrinsic nature of chemoresistance, there is only limited systemic therapy available for the patients. Vitamin E (VE) has been under intensive study as a chemopreventive agent for various types of cancers. Preclinical studies suggest that vitamin E succinate (VES) is the most effective antitumor analogue of VE, yet there are scarce studies of VES in prostate cancer. In this study, we investigated the effects of VES on a panel of prostate cancer cells, and a xenograft model of prostate cancer. Our results indicate that VES significantly inhibited proliferation and induced apoptosis of prostate cancer cell lines in a dose and time dependent manner. The results of microarray analysis followed by real-time RT-PCR and inhibitor analyses indicated that the VES-induced apoptosis is mediated by caspase-4 in prostate tumor cells. In our animal model of prostate cancer in SCID mouse, daily injection of VES significantly suppressed tumor growth as well as lung metastases. These results suggest a potential therapeutic utility of VES for patients with prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Caspases / biosynthesis
  • Caspases / metabolism
  • Caspases, Initiator
  • Cell Proliferation / drug effects
  • Gene Expression Profiling
  • Humans
  • Male
  • Mice
  • Mice, SCID
  • Oligonucleotide Array Sequence Analysis
  • Prostatic Neoplasms / pathology*
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tocopherols
  • Transplantation, Heterologous
  • Tumor Cells, Cultured
  • Vitamin E / analogs & derivatives*
  • Vitamin E / pharmacology

Substances

  • Vitamin E
  • CASP4 protein, human
  • Caspases
  • Caspases, Initiator
  • Tocopherols