Suppressive effects of a phytochemical cocktail on prostate cancer growth in vitro and in vivo Free

A104

Inflammation is implicated in the etiology of prostate cancer [1]. Evidence linking inflammation to prostate cancer includes men with chronic or recurrent inflammation of the prostate having an increased risk of developing prostate cancer [2], over-expression of inflammatory cytokines in serum and prostate tissue of prostate cancer patients and a decreased prostate cancer risk in men on non-steroidal anti-inflammatory drugs. Numerous phytochemicals have been reported to interfere with specific stages of the carcinogenic process [3]. Some of these phytochemicals like curcumin induces apoptosis and cell cycle arrest in prostate cancer cells [4] while green tea has been shown to inhibit prostate cancer development and distant site metastasis in TRAMP mice [5]. Similarly, resveratrol has also been associated with inhibition of various cancers. Based on the premise that a wide range of phytochemicals in a single formulation are likely to demonstrate greater reduction in cancer cell proliferation than individual molecules administered alone, we investigated the in vitro and in vivo effects of an antioxidant cocktail, Blueberry Punch (BBP*; Dr Red Nutraceuticals Pty Ltd), that incorporates the above mentioned phytoconstituents, in prostate cancer.
 >Cell viability studies undertaken using the MTS assay on prostate cancer cells (PC3, LNCaP) after 72 hours of exposure to increasing concentrations (0.08% - 5%) of BBP showed a dose-dependent reduction compared with untreated cells. This reduction in cell viability appeared around doses of 0.3%-0.6% BBP. Exposure of non-cancer prostate epithelial cells (PrEC) to similar concentrations demonstrated resistance of cells to BBP. Immunostaining of BBP treated cells indicated reduced COX-2 and phospho- cPLA2 protein levels. For in vivo studies, PC3 xenografts were created in immune-deficient nude Balb/C mice 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 decreased by 25% compared with mice (n = 8) that were administered regular tap water as control. Preliminary immunohistochemical analysis revealed decreased levels of Cyclin D1 protein suggesting reduced cell proliferation in BBP administered xenografts compared with vehicle treated mice. 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.
 >1. Nelson et al (2003) NEJM, 349; 366-81
 >2. Nelson et al (2004) J Urol, 172; S6-S12
 >3. Surh YJ (2003) Nat Rev Cancer, 3; 768-780
 >4. Khor et al (2006) Cancer Res, 66; 613-21
 >5. Gupta (2001) PNAS, 98; 10350-10355
 >* Antioxidant enriched fruit juice concentrate. Ingredients - Fruit juice concentrates (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.