Vitamin E succinate inhibits NF-kappaB and prevents the development of a metastatic phenotype in prostate cancer cells: implications for chemoprevention.
BACKGROUND
NF-kappaB 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-kappaB 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 alpha-tocopherol succinate (VES) inhibits NF-kappaB 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.
Crispen
Paul L
PL
Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Uzzo
Robert G
RG
Golovine
Konstantin
K
Makhov
Peter
P
Pollack
Alan
A
Horwitz
Eric M
EM
Greenberg
Richard E
RE
Kolenko
Vladimir M
VM
D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D024505:Tocopherols; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D016328:NF-kappa B; D009363:Neoplasm Proteins; D018808:Transcription Factor AP-1; D014810:Vitamin E; D024505:Tocopherols