title: An exochelin of Mycobacterium tuberculosis reversibly arrests growth of human vascular smooth muscle cells in vitro.
abstract: Proliferation of vascular smooth muscle cells (VSMC) is characteristic of restenosis following balloon angioplasty. We show here that a low concentration of a novel iron chelator, desferri-exochelin 772SM, reversibly arrests the growth of human VSMC in vitro, specifically in G(0)/G(1) and S phases. The lipophilic desferri-exochelin is effective more rapidly and at a 10-fold lower concentration than the nonlipophilic iron chelator deferoxamine. Treatment of growth-synchronized VSMC with the desferri-exochelin results in down-regulation of cyclin E/ Cdk2 and cyclin A/Cdk2 activity but does not affect the cyclin D/Cdk4/retinoblastoma phosphorylation pathway. Both DNA replication and RNA transcription are inhibited in exochelin-treated cells, but protein synthesis is not. The ability of desferri-exochelin 772SM to reversibly block the growth of VSMC in vitro with no apparent cytotoxicity suggests that the exochelin may be useful as a therapeutic agent to limit restenosis in injured vessels.
authors.affiliation: Division of Cardiology, Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
authors.forename: P M
authors.initials: PM
authors.lastname: Pahl
authors.forename: X D
authors.initials: XD
authors.lastname: Yan
authors.forename: Y K
authors.initials: YK
authors.lastname: Hodges
authors.forename: E A
authors.initials: EA
authors.lastname: Rosenthal
authors.forename: M A
authors.initials: MA
authors.lastname: Horwitz
authors.forename: L D
authors.initials: LD
authors.lastname: Horwitz
mesh_terms: D001011:Aorta; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D019927:Cyclin E / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005290:Ferric Compounds / Q000494:pharmacology*; D006801:Humans; D007083:Iliac Artery; D007502:Iron Chelating Agents / Q000494:pharmacology*; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects; D009169:Mycobacterium tuberculosis; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D012501:Saphenous Vein
chemical_list: D019927:Cyclin E; D005290:Ferric Compounds; D007502:Iron Chelating Agents; D010456:Peptides, Cyclic; D016160:Retinoblastoma Protein; C410730:desferriexochelin 772SM; C016451:ferriexochelin; D004815:Epidermal Growth Factor; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D003676:Deferoxamine