Vitamin E succinate promotes prostate tumor dormancy

MP Malafa, MD,a FD Fokum, PhDa, J Andoh, BSa, LT Neitzel, MSa, G Goodarzi PhDb, K Watabe PhDb

aDept. of Surgery,Southern Illinois University School of Medicine, Springfield, Illinois United States bDept. of Microbiology and Immunology, Southern Illinois University School of Medicine, Springfield, Illinois United States

AIM: Vitamin E succinate (VES), an ester analogue of vitamin E, selectively inhibits growth of cancer cells in vitro. Recently, we reported promotion of breast and melanoma tumor dormancy by VES. Inhibition of prostate cancer cells in vitro has been reported, but no data exist on the effects of VES on prostate cancer growth in vivo. We investigated the effects of VES on a panel of prostate cancer cells, and a xenograft model of prostate cancer. METHODS: VES effects on proliferation and apoptosis in ALVA, DU145, PC3, and AT6.1 prostate cancer cells were determined in vitro by MTS assay and cell death detection ELISA, respectively. VES effect on prostate tumor growth was measured in a model of AT6.1 prostate cancer xenografted in SCID mice. RESULTS: VES inhibited proliferation and induced apoptosis of all prostate cancer cell lines in a dose and time dependent manner. This effect was specific for the intact VES molecule. VES (150mg/kg/day) suppressed AT6.1 prostate cancer tumor growth in SCID mice before (P=0.028) and after (P=0.026) the establishment of prostate tumors. At a dose range of 50-150 mg/kg/day, the anti tumor effects of VES on established AT6.1 prostate tumor growth was dose independent. VES antitumor effect in vivo was associated with a significant increase in prostate cancer apoptosis (P=0.037). CONCLUSIONS: This first report of VES inhibition of prostate cancer growth in vivo supports future investigation of VES as a preventive and therapeutic micronutrient against prostate cancer.

KEY WORDS: prostate cancer inhibition, preventive and therapeutic micronutrient, apoptosis, proliferation.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Dietary Influences.