Celecoxib enhances the anti-Inflammatory effects of farnesylthiosalicylic acid on T cells independent of prostaglandin E2 production

Adam Mor; Elizabeta Aizman; Yoel Kloog

doi:10.1007/s10753-012-9488-8

Celecoxib enhances the anti-Inflammatory effects of farnesylthiosalicylic acid on T cells independent of prostaglandin E2 production

Adam Mor^*, Elizabeta Aizman, Yoel Kloog

^*Corresponding author for this work

Department of Neurobiology

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	1706-1714
Number of pages	9
Journal	Inflammation
Volume	35
Issue number	5
DOIs	https://doi.org/10.1007/s10753-012-9488-8
State	Published - Oct 2012

Funding

Funders	Funder number
Prajs–Drimmer Institute for the Development of Anti-degenerative Drugs
Israel Science Foundation	662/10

Keywords

Celecoxib
FTS
Ras
T cells

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s10753-012-9488-8

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title = "Celecoxib enhances the anti-Inflammatory effects of farnesylthiosalicylic acid on T cells independent of prostaglandin E2 production",

abstract = "Celecoxib (Celebrex{\textregistered}), 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{\textregistered}), 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.",

keywords = "Celecoxib, FTS, Ras, T cells",

author = "Adam Mor and Elizabeta Aizman and Yoel Kloog",

note = "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.",

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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

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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.

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Celecoxib enhances the anti-Inflammatory effects of farnesylthiosalicylic acid on T cells independent of prostaglandin E2 production

Abstract

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Keywords

UN SDGs

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