title: Nomilin inhibits tumor-specific angiogenesis by downregulating VEGF, NO and proinflammatory cytokine profile and also by inhibiting the activation of MMP-2 and MMP-9.
abstract: Angiogenesis is a crucial step in the growth and metastasis of cancers. Antiangiogenic activity of nomilin was studied using in vivo as well as in vitro models. Nomilin significantly inhibited tumor directed capillary formation. Serum proinflammatory cytokines such as IL-1β, IL-6, TNF-α and GM-CSF and also serum NO levels were significantly reduced by the treatment of nomilin. Administration of nomilin significantly reduced the serum level of VEGF, a proangiogenic factor and increased the antiangiogenic factors IL-2 and TIMP-1. In vitro studies using rat aortic ring assay showed that administration of nomilin at non-toxic concentrations significantly inhibited microvessel sprouting. Studies using human umbilical vein endothelial cells clearly demonstrated that administration of nomilin significantly retarded endothelial cell proliferation, migration, invasion and tube formation. These data clearly demonstrate the antiangiogenic potential of nomilin by downregulating the activation of MMPs, production of VEGF, NO and proinflammatory cytokines as well as upregulating IL-2 and TIMP.
authors.affiliation: Department of Immunology, Amala Cancer Research Centre, Amala Nagar, Thrissur, Kerala State 680555, India.
authors.forename: Poyil
authors.initials: P
authors.lastname: Pratheeshkumar
authors.forename: Girija
authors.initials: G
authors.lastname: Kuttan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001584:Benzoxepins / Q000494:pharmacology* / Q000627:therapeutic use; D002196:Capillaries / Q000187:drug effects / Q000503:physiopathology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D017364:Collagenases / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005780:Gelatin / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D036701:Limonins / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000098:blood supply*; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D001584:Benzoxepins; D016207:Cytokines; D036701:Limonins; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D005780:Gelatin; C059405:nomilin; D017364:Collagenases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9