Retardation of Prostate Cancer Growth In Vitro and In Vivo by a Dietary Phytochemical Cocktail

Numerous phytochemicals have been reported to interfere with specific stages of the carcinogenic process [1]. Some of these phytochemicals like curcumin induce apoptosis and cell cycle arrest in prostate cancer cells [2] while green tea has been shown to inhibit prostate cancer development and distant site metastasis in TRAMP mice [3]. Similarly, resveratrol has also been associated with inhibition of various cancers. Based on the premise that a combination of phytochemicals in the dietary form is likely to be as effective as individual molecules in reducing cancer cell proliferation, we investigated the in vitro and in vivo effects of a dietary cocktail, Blueberry Punch (BBP*; Dr Red Nutraceuticals Pty Ltd, Queensland, Australia), that incorporates the above mentioned phytoconstituents, on prostate cancer growth.

Prostate cancer cell (PC3, LNCaP) growth showed a dose-dependent reduction compared with untreated cells after 72 hours of exposure to increasing concentrations (0.08% - 5%) of BBP. This reduction in cell growth was due to decreased DNA synthesis as evaluated by 3H-thymdine incorporation. Non-cancer prostate epithelial cells (PrEC) exposed to same concentrations of BBP demonstrated resistance in terms of cell growth reduction. Exposing cancer cells to varying concentrations of mannitol indicated that the observed effects on cancer cell growth were independent of osmolarity. Immunostaining of BBP treated cells indicated reduced phospho Akt, cyclooxygenase and phospho-cytosolic phospholipase A2 levels. For in vivo studies, immunodeficient nude Balb/C mice were inoculated with 5x105 prostate cancer cells (PC-3) and treatment commenced when the tumors reached between 150-200mm3. Mice (n = 8) were administered BBP (10%) in drinking water for two weeks and tumor size and body weights monitored twice per week. At two weeks of treatment the tumor size showed a significant decrease (p=0.004, by two-way ANOVA with repeated measures) compared with mice (n = 8) that were administered regular tap water. Our data provide evidence for in vitro and in vivo suppressive effects of BBP on prostate cancer cell growth. Further studies to determine the mechanistic pathways involved in the inhibition of cancer cell growth are in progress.

* BBP Ingredients – Fruit juice concentrate (blueberry, red grapes, raspberry and elderberry), grape seed and skin extract, citrus skin extracts, green tea extract, olive leaf/olive pulp extracts, tarragon, turmeric and ginger.

1. Surh YJ (2003) Nat Rev Cancer, 3; 768-780
2. Khor et al (2006) Cancer Res, 66; 613-21
3. Gupta (2001) PNAS, 98; 10350-10355

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