Bisacurone inhibits adhesion of inflammatory monocytes or cancer cells to endothelial cells through down-regulation of VCAM-1 expression.
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.
Sun
Dong-Il
DI
Department of Otolaryngology, Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
Nizamutdinova
Irina Tsoy
IT
Kim
Young Min
YM
Cai
Xing Fu
XF
Lee
Jung Joon
JJ
Kang
Sam Sik
SS
Kim
Yeong Shik
YS
Kang
Ki Mun
KM
Chai
Gyu Young
GY
Chang
Ki Churl
KC
Kim
Hye Jung
HJ
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*
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