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.