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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.
AuthorsDong-Il Sun, Irina Tsoy Nizamutdinova, Young Min Kim, Xing Fu Cai, Jung Joon Lee, Sam Sik Kang, Yeong Shik Kim, Ki Mun Kang, Gyu Young Chai, Ki Churl Chang, Hye Jung Kim
JournalInternational immunopharmacology (Int Immunopharmacol) Vol. 8 Issue 9 Pg. 1272-81 (Sep 2008) ISSN: 1567-5769 [Print] Netherlands
PMID18602074 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclohexanols
  • Oxidants
  • Plant Extracts
  • Sesquiterpenes
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • bisacurone
  • Luciferases
  • Oncogene Protein v-akt
  • Protein Kinase C
  • Extracellular Signal-Regulated MAP Kinases
Topics
  • Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
  • Blotting, Western
  • Cell Adhesion (drug effects)
  • Cells, Cultured
  • Cyclohexanols (pharmacology)
  • Down-Regulation (drug effects)
  • Endothelial Cells (metabolism, pathology)
  • Extracellular Signal-Regulated MAP Kinases (biosynthesis, genetics)
  • Genes, Reporter
  • Humans
  • Inflammation (metabolism, pathology)
  • Luciferases (genetics)
  • Monocytes (drug effects)
  • Oncogene Protein v-akt (biosynthesis, genetics)
  • Oxidants (metabolism)
  • Plant Extracts (chemistry, pharmacology)
  • Plasmids (genetics)
  • Protein Kinase C (biosynthesis, genetics)
  • Sesquiterpenes (pharmacology)
  • Transfection
  • Tumor Necrosis Factor-alpha (biosynthesis, pharmacology)
  • Vascular Cell Adhesion Molecule-1 (biosynthesis)

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