Impact of glafenine hydrochloride on human endothelial cells and human vascular smooth muscle cells: a substance reducing proliferation, migration and extracellular matrix synthesis.
The aim of this study was to examine the effects of glafenine hydrochloride (a nonsteroidal anti-inflammatory drug) on proliferation, clonogenic activity, cell-cycle, migration, and the extracellular matrix protein tenascin of human aortic smooth muscle cells (haSMCs) and human endothelial cells (ECs) in vitro.HaSMCs and ECs were seeded in tissue culture flasks. The cells were treated for 4 days with glafenine hydrochloride (10 microM, 50 microM, 100 microM). Half of the treated groups were incubated again with glafenine hydrochloride, the other half received medium free of glafenine hydrochloride every 4 days until day 20. The growth kinetics and clonogenic activity were assessed. Cell cycle distribution was investigated by FACS, migratory ability was evaluated, and effects on extracellular matrix synthesis were assessed by immunofluorescence. Glafenine hydrochloride inhibited the proliferation and clonogenic activity of haSMCs and ECs in a dose-dependent manner. A block in the G2/M phase and a reduction in the G1 phase occurred. The migratory ability of haSMCs was impaired in a dose-dependent manner and the extracellular matrix protein tenascin was reduced. As glafenine hydrochloride has the ability to fully inhibit proliferation and to partially inhibit migration in haSMCs, it could be an interesting substance for further research in the field of restenosis therapy.
Schöber
Wolfgang
W
Eberhard-Karls-Universität, Department of Diagnostic Radiology, Hoppe-Seyler-Str. 3, Tübingen 72076, Germany. Schoeber.wogi@t-online.de
Tran
Quoc Bao
QB
Muringaseril
Matthew
M
Wiskirchen
Jakub
J
Kehlbach
Rainer
R
Rodegerdts
Enno
E
Wiesinger
Benjamin
B
Claussen
Claus D
CD
Duda
Stephan H
SH
D000199:Actins / Q000737:chemistry; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D002453:Cell Cycle; D002455:Cell Division; D002465:Cell Movement; D002469:Cell Separation; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects*; D005109:Extracellular Matrix / Q000378:metabolism*; D005434:Flow Cytometry; D005897:Glafenine / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D013997:Time Factors
D000199:Actins; D018712:Analgesics, Non-Narcotic; D005897:Glafenine; D007770:L-Lactate Dehydrogenase