Studies employing mainly in vitro tumor models show that extracts and compounds isolated from cranberry fruit (Vaccinium macrocarpon) inhibit the growth and proliferation of several types of tumor including breast, colon, prostate, and lung. Proanthocyanidin oligomers, flavonol and anthocyanin glycosides and triterpenoids are all likely contributors to the observed anticancer properties and may act in a complementary fashion to limit carcinogenesis. Possible chemopreventive mechanisms of action by cranberry phytochemicals include induction of apoptosis in tumor cells, reduced ornithine decarboxylase activity, decreased expression of matrix metalloproteinases associated with prostate tumor metastasis, and anti-inflammatory activities including inhibition of cyclooxygenases. A review of recent studies suggests a potential role for cranberry as a dietary chemopreventive and provides direction for future research.

Diets rich in fruits and vegetables have been shown to improve patient prognosis in a variety of cancers, a benefit partly derived from phytochemicals, many of which target cell death pathways in tumor cells. Cranberries (Vaccinium macrocarpon) are a phytochemical-rich fruit containing a variety of polyphenolic compounds. As flavonoids have been shown to induce apoptosis in human tumor cells, this study investigated the hypothesis that cranberry-mediated cytotoxicity in DU145 human prostate adenocarcinoma cells involves apoptosis. The results showed that induction of apoptosis in these cells occurred in response to treatment with whole cranberry extract and occurred through caspase-8 mediated cleavage of Bid protein to truncated Bid resulting in cytochrome-C release from the mitochondria. Subsequent activation of caspase-9 ultimately resulted in cell death as characterized by DNA fragmentation. Increased Par-4 protein expression was observed, and this is suggested to be at least partly responsible for caspase-8 activation. Proanthocyanidin-enriched and flavonol-enriched fractions of cranberry also increased caspase-8 and caspase-9 activity, suggesting that these compounds play a possible role in apoptosis induction. These findings indicate that cranberry phytochemicals can induce apoptosis in prostate cancer cells in vitro, and these findings further establish the potential value of cranberry phytochemicals as possible agents against prostate cancer.

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Antioxidants have been widely studied in various naturally occurring substances as a bioavailable cancer prevention treatment. Proanthocyanidins (PACs), which are abundant polyphenols in Early Black (EB) Cranberry (Vaccinium macrocarpon), are readily available and we have shown their anticancer activity in several cancer cell lines. This work focused on the activity of these compounds when incorporated into the zebrafish (Danio rerio) system. We began investigating the in vivo effect of these phytochemicals, the protective role of several other cranberry compounds, and the metabolic activity of the vertebrate model organism. Proanthocyanidin fractions were separated from fresh EB Cranberry fruit by chromatography on Sephadex LH-20 in order to acquire a workable stock solution in DMSO. Various concentrations of proanthocyanidins in solution were tested against fish ranging in age from 1-cell stage to adult level of growth. Acridine orange apoptosis indicator dye was incorporated into the treatment protocol, and it was observed that irregular epithelial cell death was occurring in treated embryos but not in the control group. Further apoptosis assays were carried out utilizing Dihydroethidium (DHE) superoxide sensitive dye in the treatment protocol. Fluorescing red nuclei were visible along the outer surface of the epithelium cell layer; an indication of superoxide release within cells leading to the nicking of DNA within the nucleus. It was also possible to screen for superoxide release in PACs treated CCD-CO18 and HT-29 cells using confocal microscopy and cell apoptosis was investigated by trypan blue cytotoxicity assay; cell apoptosis results were statistically significant as confirmed by ANOVA analysis. Results indicate that the phytochemicals may induce apoptosis in rapidly dividing cells.

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