title: Inhibition of smooth muscle cell proliferation by a chemically modified tetracycline.
abstract: BACKGROUND
  Chemically modified tetracyclines (CMTs) are a group of nonantimicrobial derivatives of tetracycline, which exert antiproliferative and anticollagenolytic properties. The molecular mechanisms, however, are poorly understood.
  
  
  METHODS
  The effect of CMT-3 on cultured, subconfluent rat aortic smooth muscle cells (SMCs) was analyzed by [(3)H]-thymidine incorporation, counting cell numbers, and flow cytometry analysis.
  
  
  RESULTS
  CMT-3 inhibited the incorporation of [(3)H]-thymidine and reduced the cell number dose-dependently, with approximately 60% inhibition at the maximal CMT-3 concentration used (20 mumol/l). CMT-3 decreased the SMC proportion in S-phase and gradually increased the proportion at G2/M. Initially, the proportion of cells in G1-phase increased and then gradually decreased back to baseline as the CMT-3 concentration increased. CMT-3 treatment of confluent SMCs for 24 h did not induce apoptosis.
  
  
  CONCLUSIONS
  CMT-3 inhibited SMC proliferation by inducing cell cycle arrest at the G2/M restriction point. Nonetheless, CMT-3 did not induce SMC apoptosis.
authors.affiliation: Wihuri Research Institute, Helsinki, Finland.
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Leskinen
authors.forename: Kari K
authors.initials: KK
authors.lastname: Eklund
authors.forename: Timo
authors.initials: T
authors.lastname: Sorsa
authors.forename: Lorne M
authors.initials: LM
authors.lastname: Golub
authors.forename: Petri T
authors.initials: PT
authors.lastname: Kovanen
authors.forename: Ken A
authors.initials: KA
authors.lastname: Lindstedt
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004261:DNA Replication; D005434:Flow Cytometry; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013752:Tetracycline / Q000494:pharmacology*
chemical_list: D013752:Tetracycline