Research: CRISPEN and COLLEAGUES,

Listed in Issue 154

Abstract

CRISPEN and COLLEAGUES, Fox Chase Cancer Center, Philadelphia, PA 19111, USA studied the interaction with and modulation of Vitamin E succinate upon transcriptional factors involved in the development and progression of prostate cancer.

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.

Methodology

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.

Conclusion

Our findings propose a potential mechanism of VES-mediated anti-tumour activity and support the role of vitamin E analogs as potential chemopreventative agents against prostate cancer.

References

Crispen PL, Uzzo RG,  Golovine K,  Makhov P,  Pollack A,  Horwitz EM, Greenberg RE, Kolenko VM. Vitamin E succinate inhibits NF-kappaB and prevents the development of a metastatic phenotype in prostate cancer cells: implications for chemoprevention. Prostate.  67(6):582-90, May 1 2007.

Comment

The above studies shows how Vitamin E succinate interacts in different ways with the complex array of genes involved in the development and progression of prostate cancer – genes involved in proliferation, apoptosis, angiogenesia and metastasis.

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