ANAHEIM, CA (UroToday.com) - Many high quality posters were presented in the Prostate Cancer Basic Research I session at the AUA. Some are highlighted herein.

"Evaluation of Pomegranate Polyphenol-Mediated Suppression of Nuclear Factor KAPPA B (NF-κB) Activity in Prostate Cancer Cell Lines"(ABSTR 1371) Matthew B Rettig, MD and associates (Veterans Affairs Greater Los Angeles Healthcare System and University of California, Los Angeles) investigated pomegranate juice, a potent antioxidant due to its polyphenol content. Pomegranate juice has demonstrated anti-proliferative and pro-apoptotic effects in prostate cancer. The authors evaluated the effects of pomegranate polyphenols on the NF-κB pathway in prostate cancer. They did this by determining the effect of pomegranate juice on the proliferation of androgen sensitive and androgen refractory prostate cancer cell lines (DU145, LNCaP, CL1, LAPC-4). The effect of pomegranate extract treatment on NF-κB activation following TNFα stimulation was measured in nuclear extracts by gel shift electrophoretic mobility shift (EMSA) analysis. NF-κB activity was further measured by a transient transfection assay. IκB protein expression was measured by western blotting with phosphorylation specific antibodies to IκBα of whole cell extracts.

The data revealed that pomegranate extract had 20 fold greater effects on cell viability compared to pomegranate juice, with a LD50 in hormone refractory CL1 and DU145 cells occurring at a dilution of 1/500-1/1000, and with 75% reduction in cell viability at 1/50. At 1/500 dilution, viability of hormone sensitive LAPC-4 cells was reduced by 75%. Nuclear localization of TNF? stimulated NF-κB expression by EMSA showed significant decrease in NF-κB activity in CL1 after 4 hours of pomegranate extract incubation, and complete abrogation of NF-κB in the constitutively expressing DU145 cells after 2 hours. Western blots of DU145 displayed a time dependent restoration of IκB levels by pomegranate extract following TNFα exposure. At a 1/1000 dilution, pomegranate extract decreased NF-κB activity measured in transient transfection assay in all cell lines.

The researchers conclude that pomegranate polyphenols significantly impact prostate cancer cell proliferation and modulate the NF-κB pathway, with both inhibition of nuclear NF-κB activity and restoration of IκB levels following TNFα mediated inhibition.

The poster "A No-Carbohydrate Diet Significantly Delays Prostate Cancer Growth in an Animal Model" (ABSTR 1451) presented by Stephen J Freedland, MD, and collaborators (Duke University, The Johns Hopkins University School of Medicine and UCLA - David Geffen School of Medicine) evaluated the hypothesis that an isocaloric no-carbohydrate ketogenic diet (NCKD) might delay prostate cancer growth in a xenograft model.

75 male SCID mice were fed one of three diets: low-fat (12% fat kcals), Western (40% fat kcals), or a NCKD (85% fat, 0% carbohydrate kcals) with the fat source being saturated fat. Mice were fed equal calories among the groups. After a 24 day run-in period, all mice were injected subcutaneously in the flank with 1 x 10⁵ LAPC-4 cells in Matrigel. Tumor volumes were recorded and mice sacrificed when tumors approached 1cc. Serum hormones levels were assessed by ELISA.

Results demonstrated that mice fed the NCKD, lost significant amounts of weight (up to 15% of body weight) relative to the low-fat and Western diet fed mice and required extra calories to equalize their body weight with the mice in the other dietary groups. Dietary treatment was significantly associated with survival, with the longest survival among the NCKD mice followed by the low-fat mice. Serum insulin and IGF-1 levels were highest among the Western diet group. The NCKD was associated with significantly decreased fatty infiltration in the liver. With the exception of weight loss in the NCKD group, no other toxicity of the diets was noted.

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Written by Christopher P. Evans, MD, a Contributing Editor with UroToday.

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