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Indatraline inhibits Rho- and calcium-mediated glioblastoma cell motility and angiogenesis.

Abstract
Glioblastoma multiforme (GBM) is the most common and lethal primary brain tumor of the central nervous system (CNS). As an attempt to identify drugs for GBM therapeutics, phenotypic assays were used to screen 1000 chemicals from a clinical compound library. GBM subtypes exhibited different capabilities to induce angiogenesis when cultured on Matrigel; proneural cells migrated and formed a tube-like structure without endothelial cells. Among the compounds screened, indatraline, a nonselective monoamine transporter inhibitor, suppressed these morphological changes; it dose dependently inhibited cell spreading, migration, and in vitro/in vivo tube formation. In addition to intracellular calcium concentration, indatraline increased the level of Rho GTPase and its activity. Moreover, indatraline downregulated angiogenesis-related genes such as IGFBP2, PTN, VEGFA, PDGFRA, and VEGFR as well as nestin, a stem cell marker. These findings collectively suggest that the activation of Rho GTPase and the suppression of angiogenesis-related factors mediate the antiangiogenic activity of indatraline in proneural GBM culture.
AuthorsJin-Chul Heo, Tae-Hoon Jung, Dae-Young Jung, Woo Kyu Park, Heeyeong Cho
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 443 Issue 2 Pg. 749-55 (Jan 10 2014) ISSN: 1090-2104 [Electronic] United States
PMID24333442 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2013 Elsevier Inc. All rights reserved.
Chemical References
  • Angiogenic Proteins
  • Indans
  • Methylamines
  • indatraline
  • rho GTP-Binding Proteins
  • Calcium
Topics
  • Angiogenic Proteins (metabolism)
  • Calcium (metabolism)
  • Cell Movement (drug effects)
  • Down-Regulation (drug effects)
  • Glioblastoma (complications, metabolism)
  • Humans
  • Indans (pharmacology)
  • Methylamines (pharmacology)
  • Neovascularization, Pathologic (complications, metabolism)
  • Tumor Cells, Cultured
  • rho GTP-Binding Proteins (metabolism)

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