Anti-angiogenic and anti-inflammatory properties of kahweol, a coffee diterpene
- Authors
- Cárdenas, C., Quesada, A.R., and Medina, M.A.
- ID
- ZDB-PUB-110823-28
- Date
- 2011
- Source
- PLoS One 6(8): e23407 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Angiogenesis Inhibitors/chemistry
- Angiogenesis Inhibitors/pharmacology*
- Animals
- Anti-Inflammatory Agents/chemistry
- Anti-Inflammatory Agents/pharmacology*
- Aorta/drug effects
- Aorta/physiology
- Apoptosis/drug effects
- Cell Movement/drug effects
- Cell Proliferation/drug effects
- Cells, Cultured
- Chemokine CCL2/metabolism
- Chick Embryo
- Chorioallantoic Membrane/blood supply
- Chorioallantoic Membrane/cytology
- Chorioallantoic Membrane/drug effects
- Coffee/chemistry*
- Cyclooxygenase 2/metabolism
- Diterpenes/chemistry
- Diterpenes/pharmacology*
- Dose-Response Relationship, Drug
- Endothelial Cells/drug effects
- Endothelial Cells/metabolism
- Endothelial Cells/physiology
- Humans
- In Vitro Techniques
- Matrix Metalloproteinase 2/metabolism
- Mice
- Mice, Inbred C57BL
- Molecular Structure
- Neovascularization, Physiologic/drug effects
- Quail
- Urokinase-Type Plasminogen Activator/metabolism
- Zebrafish
- PubMed
- 21858104 Full text @ PLoS One
Background
Epidemiological studies have shown that unfiltered coffee consumption is associated with a low incidence of cancer. This study aims to identify the effects of kahweol, an antioxidant diterpene contained in unfiltered coffee, on angiogenesis and key inflammatory molecules.
Methodology/Principal Findings
The experimental procedures included in vivo angiogenesis assays (both the chicken and quail choriallantoic membrane assay and the angiogenesis assay with fluorescent zebrafish), the ex vivo mouse aortic ring assay and the in vitro analysis of the effects of treatment of human endothelial cells with kahweol in cell growth, cell viability, cell migration and zymographic assays, as well as the tube formation assay on Matrigel. Additionally, two inflammation markers were determined, namely, the expression levels of cyclooxygenase 2 and the levels of secreted monocyte chemoattractant protein-1. We show for the first time that kahweol is an anti-angiogenic compound with inhibitory effects in two in vivo and one ex vivo angiogenesis models, with effects on specific steps of the angiogenic process: endothelial cell proliferation, migration, invasion and tube formation on Matrigel. We also demonstrate the inhibitory effect of kahweol on the endothelial cell potential to remodel extracellular matrix by targeting two key molecules involved in the process, MMP-2 and uPA. Finally, the anti-inflammatory potential of this compound is demonstrated by its inhibition of both COX-2 expression and MCP-1 secretion in endothelial cells.