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Vitamin E succinate inhibits NF‐κB and prevents the development of a metastatic phenotype in prostate cancer cells: Implications for chemoprevention
Author(s) -
Crispen Paul L.,
Uzzo Robert G.,
Golovine Konstantin,
Makhov Peter,
Pollack Alan,
Horwitz Eric M.,
Greenberg Richard E.,
Kolenko Vladimir M.
Publication year - 2007
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20468
Subject(s) - lncap , cancer research , angiogenesis , prostate cancer , metastasis , propidium iodide , apoptosis , prostate , biology , cancer , medicine , programmed cell death , biochemistry
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‐X L 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. Prostate 67: 582–590, 2007. © 2007 Wiley‐Liss, Inc.