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


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.
D042846:CDC2-CDC28 Kinases; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects*; D019927:Cyclin E / Q000037:antagonists & inhibitors / Q000235:genetics; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D014810:Vitamin E / Q000494:pharmacology*
D018797:Cell Cycle Proteins; D019927:Cyclin E; D018809:Proliferating Cell Nuclear Antigen; C413374:p27 antigen; D014810:Vitamin E; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases