Acetylsalicylic acid inhibits cell proliferation by involving transforming growth factor-beta.
BACKGROUND
Acetylsalicylic acid (ASA) inhibits cell proliferation. This may be mediated by transforming growth factor-beta (TGF-beta). TGF-beta directly stops cell proliferation, restrains cells in G(0), and inhibits the uptake of platelet-derived growth factor and insulin-like growth factor. These effects are identical to those observed with ASA treatment.


RESULTS
We cultured rat thoracic aorta vascular smooth muscle cells and measured cytotoxicity, cell proliferation, cell cycle, transcription of TGF-beta1, and concentration of TGF-beta1 in supernatant medium. ASA dose-dependently restrained cells in G(0) phase with no cytotoxic effect and inhibited cell proliferation by 30.86%. Anti-TGF-beta1 reversed this inhibition by 30.21%. However, ASA treatment decreased TGF-beta1 transcription and had no significant effect on TGF-beta1 concentration.


CONCLUSIONS
TGF-beta seems to play an important role in ASA-mediated inhibition of cell proliferation. Therefore, treatment with ASA prevents coronary disease not only by means of its antiplatelet properties but also by an important inhibition of plaque growth. This relationship between ASA and TGF-beta explains many other effects, such as cancer chemoprevention, immunomodulation, and wound healing. The aim of this study was to demonstrate this link.
Redondo
Santiago
S
Department of Pharmacology, School of Medicine, Universidad Complutense, CIEMAT, Madrid, Spain.
Santos-Gallego
Carlos G
CG
Ganado
Patricia
P
García
Marta
M
Rico
Laura
L
Del Rio
Marcela
M
Tejerina
Teresa
T
D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D015152:Blotting, Northern; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D007770:L-Lactate Dehydrogenase; D001241:Aspirin