TY - JOUR
T1 - Celecoxib enhances the anti-Inflammatory effects of farnesylthiosalicylic acid on T cells independent of prostaglandin E2 production
AU - Mor, Adam
AU - Aizman, Elizabeta
AU - Kloog, Yoel
N1 - Funding Information:
This work was supported in part by The Israel Science Foundation (grant no. 662/10 awarded to Y.K.) and by the Prajs–Drimmer Institute for the Development of Anti-degenerative Drugs (Y.K. and E.A.). Y. Kloog is the incumbent of the Jack H. Skirball Chair in Applied Neurobiology. We thank S.R. Smith for editorial assistance. We are grateful to Dr. Mark Philips (NYU) for indispensible support, both with reagents and knowledge.
PY - 2012/10
Y1 - 2012/10
N2 - 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 antiinflammatory 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 E2 secretion. These data point to the promising potential of combined treatment with celecoxib and FTS for inflammatory disorders involving lymphocytes.
AB - 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 antiinflammatory 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 E2 secretion. These data point to the promising potential of combined treatment with celecoxib and FTS for inflammatory disorders involving lymphocytes.
KW - Celecoxib
KW - FTS
KW - Ras
KW - T cells
UR - http://www.scopus.com/inward/record.url?scp=84866735583&partnerID=8YFLogxK
U2 - 10.1007/s10753-012-9488-8
DO - 10.1007/s10753-012-9488-8
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
AN - SCOPUS:84866735583
SN - 0360-3997
VL - 35
SP - 1706
EP - 1714
JO - Inflammation
JF - Inflammation
IS - 5
ER -
