title: Anti-angiogenic activity of cranberry proanthocyanidins and cytotoxic             properties in ovarian cancer cells.
abstract: Cranberry extracts may provide beneficial health effects in the treatment             of various diseases, including cancer. However, the underlying molecular mechanisms             of antineoplastic properties are not understood. We report the effect of a proanthocyanidin             (PAC)-rich isolate from cranberry (PAC-1) as a therapeutic agent with dual activity             to target both ovarian cancer viability and angiogenesis in vitro. PAC-1 treatment             of chemotherapy-resistant SKOV-3 cells blocked cell cycle progression through             the G2/M phase, increased the generation of reactive oxygen species (ROS), and             induced apoptosis through activation of intrinsic and extrinsic pathway components.             Cytotoxicity of PAC-1 was partially based on ROS generation and could be blocked             by co-treatment with antioxidant glutathione. PAC-1 reduced the cell viability             of both SKOV-3 ovarian cancer cells and HUVEC endothelial cells in a dose-dependent             manner and blocked the activation of the pro-survival factor AKT. Furthermore,             PAC-1 blocked vascular endothelial growth factor (VEGF)-stimulated receptor phosphorylation             in endothelial cells, which correlated with the inhibition of endothelial tube             formation in vitro. Our findings suggest that PAC-1 exerts potent anticancer and             anti-angiogenic properties and that highly purified PAC from cranberry can be             further developed to treat ovarian cancer in combinational or single-agent therapy.
authors.affiliation: Molecular Therapeutics Laboratory, Program in Women's Oncology, Department of Obstetrics and Gynecology, Women and Infants Hospital of Rhode Island, Providence, RI 02905, USA. kkim@wihri.org
authors.forename: Kyu Kwang
authors.initials: KK
authors.lastname: Kim
authors.forename: Ajay P
authors.initials: AP
authors.lastname: Singh
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Singh
authors.forename: Angelica
authors.initials: A
authors.lastname: Demartino
authors.forename: Laurent
authors.initials: L
authors.lastname: Brard
authors.forename: Nicholi
authors.initials: N
authors.lastname: Vorsa
authors.forename: Thilo S
authors.initials: TS
authors.lastname: Lange
authors.forename: Richard G
authors.initials: RG
authors.lastname: Moore
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D020533:Angiogenesis Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects; D005260:Female; D005638:Fruit / Q000737:chemistry; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology; D044945:Proanthocyanidins / Q000302:isolation & purification / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D029799:Vaccinium macrocarpon / Q000737:chemistry
chemical_list: D020533:Angiogenesis Inhibitors; D010936:Plant Extracts; D044945:Proanthocyanidins; D017382:Reactive Oxygen Species; D040262:Receptors, Vascular Endothelial Growth Factor; D051057:Proto-Oncogene Proteins c-akt