title: Anti inflammatory and anti angiogenic effect of black raspberry extract on human esophageal and intestinal microvascular endothelial cells.
abstract: Polyphenolic compounds (anthocyanins, flavonoid glycosides) in berries prevent the initiation, promotion, and progression of carcinogenesis in rat's digestive tract and esophagus, in part, via anti-inflammatory pathways. Angiogenesis has been implicated in the pathogenesis of chronic inflammation and tumorigenesis. In this study, we investigated the anti-inflammatory and anti-angiogenic effects of black raspberry extract (BRE) on two organ specific primary human intestinal microvascular endothelial cells, (HIMEC) and human esophageal microvascular endothelial cells (HEMEC), isolated from surgically resected human intestinal and donor discarded esophagus, respectively. HEMEC and HIMEC were stimulated with TNF-α/IL-1β with or without BRE. The anti-inflammatory effects of BRE were assessed based upon COX-2, ICAM-1 and VCAM-1 gene and protein expression, PGE2 production, NFκB p65 subunit nuclear translocation as well as endothelial cell-leukocyte adhesion. The anti-angiogenic effects of BRE were assessed on cell migration, proliferation and tube formation following VEGF stimulation as well as on activation of Akt, MAPK and JNK signaling pathways. BRE inhibited TNF-α/IL-1β-induced NFκB p65 nuclear translocation, PGE2 production, up-regulation of COX-2, ICAM-1 and VCAM-1 gene and protein expression and leukocyte binding in HEMEC but not in HIMEC. BRE attenuated VEGF-induced cell migration, proliferation and tube formation in both HEMEC and HIMEC. The anti-angiogenic effect of BRE is mediated by inhibition of Akt, MAPK and JNK phosphorylations. BRE exerted differential anti-inflammatory effects between HEMEC and HIMEC following TNF-α/IL-1β activation whereas demonstrated similar anti-angiogenic effects following VEGF stimulation in both cell lines. These findings may provide more insight into the anti-tumorigenic capacities of BRE in human disease and cancer.
authors.affiliation: Department of Surgery, The Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Rituparna
authors.initials: R
authors.lastname: Medda
authors.affiliation: Division of Gastroenterology/Hepatology, The Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Orestis
authors.initials: O
authors.lastname: Lyros
authors.affiliation: Division of Gastroenterology/Hepatology, The Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Schmidt
authors.affiliation: Division of Gastroenterology/Hepatology, The Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Nebojsa
authors.initials: N
authors.lastname: Jovanovic
authors.affiliation: Department of Surgery, The Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Linghui
authors.initials: L
authors.lastname: Nie
authors.affiliation: Department of Surgery, The Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Link
authors.affiliation: Department of Surgery, The Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Mary F
authors.initials: MF
authors.lastname: Otterson
authors.affiliation: Cancer Center, The Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Gary D
authors.initials: GD
authors.lastname: Stoner
authors.affiliation: Division of Gastroenterology/Hepatology, The Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Reza
authors.initials: R
authors.lastname: Shaker
authors.affiliation: Department of Surgery, The Medical College of Wisconsin, Milwaukee, WI, USA. Electronic address: prafiee@mcw.edu.
authors.forename: Parvaneh
authors.initials: P
authors.lastname: Rafiee
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004947:Esophagus / Q000098:blood supply*; D005638:Fruit; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007422:Intestines / Q000098:blood supply*; D055806:Microvessels / Q000187:drug effects* / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010766:Phosphorylation; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D065856:Rubus; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D020533:Angiogenesis Inhibitors; D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D010936:Plant Extracts; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases
keywords: Angiogenesis; Black raspberry; HEMEC; HIMEC; Inflammation