title: Anti-angiogenic and anti-inflammatory properties of kahweol, a coffee diterpene.
abstract: 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Taken together, our data indicate that, indeed, kahweol behaves as an anti-inflammatory and anti-angiogenic compound with potential use in antitumoral therapies. These data may contribute to the explanation of the reported antitumoral effects of kahweol, including the recent epidemiological meta-analysis showing that drinking coffee could decrease the risk of certain cancers.
authors.affiliation: Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, Málaga, Spain.
authors.forename: Casimiro
authors.initials: C
authors.lastname: Cárdenas
authors.forename: Ana R
authors.initials: AR
authors.lastname: Quesada
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Medina
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000166:cytology / Q000187:drug effects; D003069:Coffee / Q000737:chemistry*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011784:Quail; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism; D015027:Zebrafish
chemical_list: D020533:Angiogenesis Inhibitors; D000893:Anti-Inflammatory Agents; D018932:Chemokine CCL2; D003069:Coffee; D004224:Diterpenes; C053401:kahweol; D051546:Cyclooxygenase 2; D014568:Urokinase-Type Plasminogen Activator; D020778:Matrix Metalloproteinase 2