2574

Prostate cancer is the most common malignancy in men and is the second leading cause of cancer-related deaths in men in the Western world. Hypoxia is commonly present within tumors and stimulates angiogenesis via induction of hypoxia-inducible factor (HIF)-1α due to the poor oxygenation resulting from tumor neovasculature. In order to determine whether a pomegranate extract (POMX) known to inhibit prostate cancer cell proliferation in vitro and in vivo can inhibit angiogenesis via inhibition of HIF-1α, prostate cancer cells (LNCaP and DU-145) and human umbilical vein endothelial cells (HUVEC) were grown under normoxic and hypoxic conditions. We further examined the effect of POMX administration over 4 weeks to immunoincompetent mice with a prostate cancer cell (LAPC-4) xenograft on growth, HIF-1α, and microvessel density. POMX suppressed the growth of LNCaP and DU-145 prostate cancer cells as well as HUVEC under both normoxic and hypoxic conditions but to a greater extent under hypoxic conditions. A decrease of HIF-1α protein expression of greater than 50% was seen at POMX concentrations of 10 μg/ml for LNCaP and DU-145, and 1 μg/ml for HUVEC under hypoxic conditions. Vascular endothelial growth factor (VEGF) levels were measured in the medium and found to be decreased under normoxic and to a greater extent under hypoxic conditions. POMX decreased prostate cancer xenograft size and the tumor vessel density after 4 weeks of treatment. Serum VEGF levels are being measured in POMX-treated mice. These data demonstrate that POMX decreases HIF-1α protein expression and inhibits the growth of prostate cancer cells as well as HUVEC under hypoxic conditions. Thus, POMX may have the potential to be used in prostate cancer treatment regimens where there is an advantage to inhibiting tumor angiogenesis, and may be effective under hypoxic conditions in tumor tissues.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

American Association for Cancer Research
2007