Antiproliferative activity of anti-inflammatory drugs in two mammalian cell culture lines.

The nonsteroid anti-inflammatory drugs inhibited cell proliferation when added to rat hepatoma and human fibroblast cultures. The inhibition was reversible; normal growth resumed when the cultures were washed free of drug. Protein and nucleic acid synthesis, as measured by isotope incorporation was also reduced, although this reduction was probably a reflection of the decrease in cell numbers. An exception was that, in low concentration, the salicylate drugs, salicylamide, salicylic acid and aspirin, stimulated protein and nucleic acid synthesis, but in high concentrations (greater than 1 mM) they inhibited culture growth as well as protein and nucleic acid synthesis. Pharmacologically inactive derivatives, such as m-hydroxybenzoic acid and gentisic acid, were not inhibitory in concentrations up to 5 mM. The order of potency in inhibiting culture growth, meclofenamate greater than indomethacin greater than salicylamide greater than phenylbutazone greater than phenacetin greater than aspirin = salicylic acid, was similar to that reported for their anti-inflammator activity and their ability to inhibit prostaglandin synthesis. The antiproliferative activity of these drugs may, in part, account for their anti-inflammatory and toxic actions in vivo.