title: Bisacurone inhibits adhesion of inflammatory monocytes or cancer cells to endothelial cells through down-regulation of VCAM-1 expression.
abstract: Bisacurone, one of the active compounds of the traditionally used indigenous herb Curcuma longa Linne (Zingiberaceae), has anti-oxidant, anti-inflammatory, and anti-metastatic activities. We studied how the level of vascular cell adhesion molecule-1 (VCAM-1), one of the key molecules in the development of atherosclerosis as well as carcinogenesis and metastasis, might be affected by bisacurone in tumor necrosis factor-alpha (TNF-alpha)-activated human umbilical vein endothelial cells (HUVECs). Bisacurone dose-dependently inhibited TNF-alpha-mediated expression of VCAM-1. It showed significant suppressive effect on ROS generation in response to TNF-alpha stimulation and it blocked nuclear factor-kappa B (NF-kappaB) p65 translocation into the nucleus and phosphorylation of inhibitory factor kappaBalpha (IkappaBalpha). It also inhibited phosphorylation of Akt and PKC, which are upstream in the regulation of VCAM-1 by TNF-alpha. Furthermore, bisacurone decreased U937 monocyte and human oral cancer cell (Hep-2, QLL-I, SCC-15) adhesion to HUVECs stimulated by TNF-alpha, suggesting that it may inhibit the binding of these cells by regulating the expression of critical adhesion molecules by TNF-alpha. Thus, bisacurone may be beneficial in the treatment of inflammatory diseases, such as atherosclerosis, where inflammatory monocytes are involved in their pathology, and, moreover, in the development of tumors.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Dong-Il
authors.initials: DI
authors.lastname: Sun
authors.forename: Irina Tsoy
authors.initials: IT
authors.lastname: Nizamutdinova
authors.forename: Young Min
authors.initials: YM
authors.lastname: Kim
authors.forename: Xing Fu
authors.initials: XF
authors.lastname: Cai
authors.forename: Jung Joon
authors.initials: JJ
authors.lastname: Lee
authors.forename: Sam Sik
authors.initials: SS
authors.lastname: Kang
authors.forename: Yeong Shik
authors.initials: YS
authors.lastname: Kim
authors.forename: Ki Mun
authors.initials: KM
authors.lastname: Kang
authors.forename: Gyu Young
authors.initials: GY
authors.lastname: Chai
authors.forename: Ki Churl
authors.initials: KC
authors.lastname: Chang
authors.forename: Hye Jung
authors.initials: HJ
authors.lastname: Kim
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D003511:Cyclohexanols / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis / Q000235:genetics; D017930:Genes, Reporter; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology*; D008156:Luciferases / Q000235:genetics; D009000:Monocytes / Q000187:drug effects*; D051058:Oncogene Protein v-akt / Q000096:biosynthesis / Q000235:genetics; D016877:Oxidants / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D010957:Plasmids / Q000235:genetics; D011493:Protein Kinase C / Q000096:biosynthesis / Q000235:genetics; D012717:Sesquiterpenes / Q000494:pharmacology*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003511:Cyclohexanols; D016877:Oxidants; D010936:Plant Extracts; D012717:Sesquiterpenes; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C531975:bisacurone; D008156:Luciferases; D051058:Oncogene Protein v-akt; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases