title: North American cranberry (Vaccinium macrocarpon) stimulates apoptotic pathways in DU145 human prostate cancer cells in vitro.
abstract: 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.
authors.affiliation: Department of Biology, University of Prince Edward Island, Charlottetown, Prince Edward Island, Canada.
authors.forename: Malcolm A
authors.initials: MA
authors.lastname: MacLean
authors.forename: Bradley E
authors.initials: BE
authors.lastname: Scott
authors.forename: Bob A
authors.initials: BA
authors.lastname: Deziel
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Nunnelley
authors.forename: Anne M
authors.initials: AM
authors.lastname: Liberty
authors.forename: Katherine T
authors.initials: KT
authors.lastname: Gottschall-Pass
authors.forename: Catherine C
authors.initials: CC
authors.lastname: Neto
authors.forename: Robert A R
authors.initials: RA
authors.lastname: Hurta
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D053938:DNA Fragmentation / Q000187:drug effects; D005419:Flavonoids / Q000032:analysis; D006801:Humans; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D029799:Vaccinium macrocarpon / Q000737:chemistry
chemical_list: D005419:Flavonoids; D010936:Plant Extracts; D053181:Caspase 8; D053453:Caspase 9