Faculty Collaboration Database

Anti inflammatory and anti angiogenic effect of black raspberry extract on human esophageal and intestinal microvascular endothelial cells. Microvasc Res 2015 Jan;97:167-80

Date

12/03/2014

Pubmed ID

25446010

Pubmed Central ID

PMC4275382

DOI

10.1016/j.mvr.2014.10.008

Scopus ID

2-s2.0-84918496923 (requires institutional sign-in at Scopus site)   57 Citations

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.

Author List

Medda R, Lyros O, Schmidt JL, Jovanovic N, Nie L, Link BJ, Otterson MF, Stoner GD, Shaker R, Rafiee P

Authors

Mary F. Otterson MD Professor in the Surgery department at Medical College of Wisconsin
Reza Shaker MD Assoc Provost, Sr Assoc Dean, Ctr Dir, Chief, Prof in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Angiogenesis Inhibitors
Animals
Anti-Inflammatory Agents
Cell Movement
Cell Proliferation
Cell Survival
Endothelial Cells
Esophagus
Fruit
Humans
Inflammation Mediators
Intestines
Microvessels
Mitogen-Activated Protein Kinases
Neovascularization, Physiologic
Phosphorylation
Phytotherapy
Plant Extracts
Plants, Medicinal
Proto-Oncogene Proteins c-akt
Rubus
Signal Transduction
Time Factors