Modulation of cell proliferation and cell cycle regulators by vitamin E in human prostate carcinoma cell lines

J Urol. 2002 Oct;168(4 Pt 1):1578-82. doi: 10.1097/01.ju.0000030156.80151.bb.

Abstract

Purpose: Vitamin E has been identified as a candidate agent for the prevention of prostate cancer. We hypothesize that the mechanism for this effect is in part a result of cell cycle inhibition rather than only due to a reduction in reactive oxygen species. We tested whether vitamin E induces cell cycle arrest in prostate carcinoma, mediated by alterations in cell cycle regulatory proteins, including cyclin E, cdk2 and p27.

Materials and methods: Cells were incubated with and without vitamin E (alpha-tocopherol succinate, 20 microg./ml.), fixed and stained with propidium iodide for flow cytometry analysis. In parallel experiments total protein was extracted, immunoprecipitated with cyclin E antibody and analyzed by Western blot for the expression of cell cycle markers.

Results: Flow cytometry analysis revealed a dramatic reduction in the S phase percent of LNCaP and PC3 cells in response to vitamin E (69% and 95%, respectively). It was accompanied by over expression of p27 (3-fold increase) with vitamin E treatment.

Conclusions: This study demonstrates that at physiological concentrations vitamin E induced profound cell cycle arrest mediated by up-regulation of p27. This observation provides a theoretical basis for the putative chemopreventive effect of vitamin E.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CDC2-CDC28 Kinases*
  • Cell Cycle Proteins / metabolism*
  • Cell Division / drug effects*
  • Cyclin E / antagonists & inhibitors
  • Cyclin E / genetics
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases / antagonists & inhibitors
  • Cyclin-Dependent Kinases / genetics
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Male
  • Proliferating Cell Nuclear Antigen / genetics
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / prevention & control
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Serine-Threonine Kinases / genetics
  • Tumor Cells, Cultured / drug effects*
  • Up-Regulation / drug effects
  • Up-Regulation / genetics
  • Vitamin E / pharmacology*

Substances

  • Cell Cycle Proteins
  • Cyclin E
  • Proliferating Cell Nuclear Antigen
  • p27 antigen
  • Vitamin E
  • Protein-Serine-Threonine Kinases
  • CDC2-CDC28 Kinases
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases