title: A Phenanthrene Derivative, 5,7-Dimethoxy-1,4-Phenanthrenequinone, Inhibits Cell Adhesion Molecule Expression and Migration in Vascular Endothelial and Smooth Muscle Cells.
abstract: The activation of endothelial cells (ECs) and migration of vascular smooth muscle cells (VSMCs) have played a crucial role in monocyte chemotaxis/adhesion and intima thickening during vascular injury and atherosclerosis, respectively. Several phenanthrenes isolated from plants and natural products have been shown to possess different bioactivities such as anti-platelet aggregation and anti-inflammation. The current study was designated to investigate the effects of a phenanthrene derivative, 5,7-dimethoxy-1,4-phenanthrenequinone (DMPQ), on cell adhesion molecule (CAM) expression in vascular ECs and migration in VSMCs. The DMPQ attenuated monocyte-EC interaction but it did not affect monocyte adhesion to matrix. In parallel, DMPQ reduced tumor necrosis factor-α (TNF-α)-induced intercellular adhesion molecule and vascular CAM expression in ECs. DMPQ compromised TNF-α-induced IκB activation, nuclear factor-kappa B (NF-κB) translocation, and NF-κB-DNA complex formation. Moreover, it affected TNF-α- and hydrogen peroxide (H2O2)-induced reactive oxygen species production and IκB activation. These suggest that DMPQ affects CAM expression by affecting NF-κB signaling. Meanwhile, DMPQ could also inhibit platelet-derived growth factor (PDGF)-induced VSMC migration toward collagen by affecting cellular PDGF signaling, including PDGFRβ, PLCγ, ERK1/2, and Akt phosphorylation. The VSMC adhesion to collagen and collagen-induced focal adhesion kinase activation during cell adhesion were impaired by DMPQ treatment. This study reveals a phenanthrene derivative-DMPQ-with anti-inflammatory and anti-migratory bioactivity toward vascular ECs and SMCs, suggesting its protective effect on vascular injuries.
authors.affiliation: School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan.
authors.forename: Huey-Ming
authors.initials: HM
authors.lastname: Lo
authors.forename: Tsong-Long
authors.initials: TL
authors.lastname: Hwang
authors.forename: Wen-Bin
authors.initials: WB
authors.lastname: Wu
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide; D020672:I-kappa B Proteins / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010616:Phenanthrenes / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors; D011809:Quinones / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology
chemical_list: C000618834:5,7-dimethoxy-1,4-phenanthrenequinone; D015815:Cell Adhesion Molecules; D020672:I-kappa B Proteins; D016328:NF-kappa B; D010616:Phenanthrenes; D010982:Platelet-Derived Growth Factor; D011809:Quinones; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D006861:Hydrogen Peroxide; D051416:Focal Adhesion Protein-Tyrosine Kinases