Vitamin E succinate inhibits NF-κB and prevents the development of a metastatic phenotype in prostate cancer cells: Implications for chemoprevention

Paul L. Crispen, Robert G. Uzzo, Konstantin Golovine, Peter Makhov, Alan Pollack, Eric M. Horwitz, Richard E. Greenberg, Vladimir M. Kolenko

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

BACKGROUND. NF-κB and AP-1 transcriptional factors contribute to the development and progression of prostate malignancy by regulating the expression of genes involved in proliferation, apoptosis, angiogenesis, and metastasis. METHODS. NF-κB and AP-1 activities were examined by TransAm assay. Cytokines levels were assessed by ELISA. ICAM-1 and gp130 expression was examined by flow cytometry. Cell adhesion was examined by the ability of cells to adhere to fibronectin-coated plates. Cell viability was determined by propidium iodide staining. RESULTS. Treatment with α-tocopherol succinate (VES) inhibits NF-κB but augments AP-1 activity, reduces expression of IL-6, IL-8, and VEGF, suppresses cell adhesion, ICAM-1 and gp130 expression in androgen-independent PC-3, DU-145, and CA-HPV-10 cells. VES supplementation also decreases the expression of anti-apoptotic XIAP and Bcl-XL proteins and sensitizes androgen-dependent LNCaP cells to androgen deprivation. CONCLUSIONS. Our findings propose a potential mechanism of VES-mediated anti-tumor activity and support the role of vitamin E analogs as potential chemopreventative agents against prostate cancer.

Original languageEnglish (US)
Pages (from-to)582-590
Number of pages9
JournalProstate
Volume67
Issue number6
DOIs
StatePublished - May 1 2007
Externally publishedYes

Keywords

  • Adhesion
  • AP-1
  • Apoptosis
  • Cytokines

ASJC Scopus subject areas

  • Urology

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