Abstract. The chemopreventive efficacy of cranberry juice concentrate in an experimental model of urinary bladder cancer was evaluated using female Fischer-344 rats. The animals received N-butyl-N-(4-hydroxybutyl)-nitrosamine (OH-BBN) for a period of eight weeks. Cranberry juice concentrate was administered at doses of 1.0 or 0.5 ml/rat/ day beginning one week after the final OH-BBN treatment and continuing until the end of the study. The urinary bladders of all the rats were weighed and examined grossly for lesions, and all masses were submitted for pathological evaluation. A dose-dependent preventive effect of cranberry treatment was observed, with a reduced number of urinary bladder cancers (38%) in the 1.0 ml/rat/day group versus the control group. The cranberry extract neither affected body weight gain nor caused other signs of toxicity. For the metabolic studies, serum and urine were collected at 4 and 12 h after the administration of the cranberry juice concentrate and were analyzed by LC-MS/MS. Quercetin and its methylated derivative were detected in the urine samples. However, no quercetin was detected in the serum samples, indicating its poor bioavailability. These data suggest that components of cranberries may be effective in preventing urinary bladder carcinogenesis.
IntroductionNumerous epidemiological data have supported the inverse relationship between the consumption of fruit and vegetables and the incidence of urinary bladder cancer (1,2). The preventive effects of green tea leaves and one of its major components, epigallocatechin gallate (EGCG), have been reported for bladder cancer (3,4). The role of diet as a cause of urinary bladder carcinogenesis is feasible since most substances and/or their metabolites (including carcinogens) are excreted through the urinary tract. Importantly, the urinary concentration of these substances is substantially higher than in other tissues, thereby, enhancing their harmful activity. Foods that also contain significant amounts of cancer-preventive components may provide desirable health benefits beyond a basic nutritional function.The American cranberry (Vaccinium macrocarpon) contains the highest percentage of polyphenols by weight among 20 fruits analyzed in a previous study (5). Cranberry juice is well known for its possible beneficial effects in urinary tract infections (UTI), and considerable attention has been given to its active components and mechanism of action in vivo (6). Quercetin (Fig. 1), one of the major phytochemicals of the cranberry, has been reported to be a growth inhibitor of primary bladder transitional cell cancers in humans (7). Cancers of the urinary bladder were not observed in rats given a 5% quercetin diet (8). Synergistic or additive antiproliferative interactions of phytochemicals in a cranberry extract have recently been reported in several human tumor cell lines (9).Cranberry juice may be active in the prevention of UTI by blocking cell proliferation. Non-steroidal anti-inflammatory drugs (NSAIDs), which have antiproliferative a...