Inhibition of the growth of 12V-ras-transformed rat fibroblasts by acetylsalicylic acid correlates with inhibition of NF-kappa B.
Epidemiological studies have demonstrated a correlation between regular aspirin (acetylsalicylic acid; ASA) use and a decreased risk for the development of cancer. We here show that ASA inhibits the growth of 12V-ras-transformed rat fibroblasts in vitro at pharmacological concentrations. This effect appeared to be unrelated to inhibition of cyclooxygenase, since other cyclooxygenase inhibitors did not inhibit cell growth. A number of nuclear transcription factors have been implicated as mediators of transformation. ASA has recently been reported to inhibit the activation of one such factor, NF-kappa B. We found that NF-kappa B binding activity was decreased in ASA-treated 12V-ras-transformed cells. Inhibition of NF-kappa B activation was not due to a general inhibitory effect, since AP-1 binding activity was not affected. We conclude that ASA inhibits the growth of 12V-ras-transformed fibroblasts, possibly via inhibition of NF-kappa B.
Ljungdahl
S
S
Department of Oncology-Pathology, Radiumhemmet, Karolinska Institute and Hospital, Stockholm, Sweden.
Shoshan
M C
MC
Linder
S
S
D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D002461:Cell Line, Transformed; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D005347:Fibroblasts / Q000378:metabolism; D011905:Genes, ras / Q000235:genetics*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics; D009363:Neoplasm Proteins / Q000737:chemistry; D051381:Rats; D018808:Transcription Factor AP-1 / Q000187:drug effects / Q000235:genetics
D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D016328:NF-kappa B; D009363:Neoplasm Proteins; D018808:Transcription Factor AP-1; D001241:Aspirin