Celecoxib enhances the anti-inflammatory effects of farnesylthiosalicylic acid on T cells independent of prostaglandin E(2) production.
Celecoxib (Celebrex(®)), a non-steroidal anti-inflammatory drug and selective cyclooxygenase-2 inhibitor, is widely used to treat arthritis and other inflammatory disorders. Awareness of its anti-proliferative properties has prompted another indication for its use, in preventing colon polyps in high-risk populations. Farnesylthiosalicylic acid (FTS; Salirasib(®)), designed to inhibit oncogenic Ras and currently under evaluation in phase I/II and II clinical trials, was recently shown by our group to exert anti-inflammatory effects on both lymphocytes and mast cells. Here we examined whether celecoxib combined with FTS would enhance this anti-inflammatory activity. While each drug separately inhibited Ras activation in these cells, their combination yielded more marked inhibition as well as further inhibition of ERK phosphorylation, lymphocyte adhesion, and interleukin-2 secretion. The inhibitory effects, moreover, were independent of prostaglandin E(2) secretion. These data point to the promising potential of combined treatment with celecoxib and FTS for inflammatory disorders involving lymphocytes.
Department of Medicine, Division of Rheumatology, New York University School of Medicine, 450 E 29th Street, New York, NY 10016, USA. Adam.Mor@NYUMC.org
Adam
A
Mor
Elizabeta
E
Aizman
Yoel
Y
Kloog
D000818:Animals; D000068579:Celecoxib; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism*; D004357:Drug Synergism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005204:Farnesol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D019169:Jurkat Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D015689:Oncogene Protein p21(ras) / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology*; D012459:Salicylates / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism
D052246:Cyclooxygenase 2 Inhibitors; D007376:Interleukin-2; D011720:Pyrazoles; D012459:Salicylates; D013449:Sulfonamides; C093323:farnesylthiosalicylic acid; D005204:Farnesol; D048049:Extracellular Signal-Regulated MAP Kinases; D015689:Oncogene Protein p21(ras); D000068579:Celecoxib; D015232:Dinoprostone