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Cited by 33Inflammatory mediators and NSAID effectsEicosanoids and Hypertension PharmacologyCancer, Lipids, and Metabolism

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Eicosanoid metabolism in squamous cell carcinoma cell lines derived from primary and metastatic head and neck cancer and its modulation by celecoxib

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Schroeder, Claudia P., Yang, Peiying, Newman, Robert A., Lotan, Reuben·2004·Cancer Biology & Therapy
DOI 10.4161/cbt.3.9.1037
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Abstract

Eicosanoid metabolism through cyclooxygenases (COXs) and lipoxygenases (LOXs) generates various lipids that play a role in squamous cell carcinogenesis. We used pairs of head and neck squamous cell carcinoma (HNSCC) cell lines derived from primary and metastatic tumors of the same patient to analyze eicosanoid metabolites by ESI-LC/MS/MS and COX/LOX expression by western immunoblotting. The effects of celecoxib on eicosanoid synthesis and HNSCC cell growth were examined. Prostaglandin E2 (PGE2) was the major metabolite in three of six cell lines. COX-2 was detected in three cell lines, which produced PGE2 (two from metastases). We found low expression of COX-1 at similar intensities for each pair of cell lines. 5-LOX was detected in all cells. Some expressed 12-LOX, 15-LOX-1, and 15-LOX-2, but there was no correlation between enzyme expression and endogenous product content. Exogenous arachidonic acid did not change the profile of eicosanoid biosynthesis. Low doses of celecoxib inhibited formation of PGE2 in UMSCC-14A cells by 84% as early as 6 hours. In contrast, 5-HETE, 12-HETE, and 15-HETE levels were increased by approximately 40-, 5- and 3-fold, respectively, with a decline to baseline levels within 24 hours. High dose celecoxib increased the 12-HETE level 2.3-fold after 3 days of incubation. Celecoxib inhibited growth of all HNSCC cell lines in a concentration-dependent manner regardless of their COX expression (IC50 values after 3 days; 33 to 62 microM). Our findings provide new informations about individual eicosanoids produced by HNSCC cells and their differential regulation by the selective COX-2 inhibitor celecoxib.

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  • Cancer cells directly inhibit the immune system through molecules such as VEGF, prostaglandin E2, TGF-β, and IL-10, which suppress cytotoxic T-cell function.

    “Cancer cells also directly inhibit the immune system through molecules like vascular endothelial growth factor (VEGF), prostaglandin E2, transforming growth factor-β (TGF- β), and interleukin-10 (IL-10), which suppress cytotoxic T-cell function [77,78,80,81,82,83].”

    From Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy (2024) · cites this paper as [81]

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Metadata

Authors
Schroeder, C. P., Yang, P., Newman, R. A., & Lotan, R.
Affiliations
The University of Texas MD Anderson Cancer Center (US)
Corresponding author
Lotan, Reuben
ORCID
Venue
Cancer Biology & Therapy
Publisher
Informa UK Limited
Published
2004-09
Volume
3
Issue
9
Pages
847-852
ISSN
  • 1538-4047 (ISSN-L)
  • 1555-8576
DOI
10.4161/cbt.3.9.1037
OpenAlex
W2010706029
Cited by
33
References
0
Citations by year
2026: 1 · 2025: 1 · 2024: 1 · 2022: 3 · 2020: 1 · 2019: 1 · 2018: 1 · 2015: 2 · 2014: 1 · 2012: 1
FWCI
2.51
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Cancer Biology & Therapy (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Defense
  • Deutsche Forschungsgemeinschaft
  • National Cancer Institute (P01 CA98144)
Topics
  • Health Sciences › Medicine › Pharmacology (medical) › Inflammatory mediators and NSAID effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Keywords
eicosanoid metabolism, head and neck squamous cell carcinoma, metastatic cancer, celecoxib, cyclooxygenase-2, cyclooxygenase-1, lipoxygenase, prostaglandin E2, 5-hydroxyeicosatetraenoic acid, 12-hydroxyeicosatetraenoic acid, 15-hydroxyeicosatetraenoic acid, COX-2 inhibition, tumor cell growth inhibition, arachidonic acid
MeSH terms
Celecoxib, Carcinoma, Squamous Cell, Dose-Response Relationship, Drug, Head and Neck Neoplasms, Humans, Lipoxygenase, Neoplasm Metastasis, Prostaglandin-Endoperoxide Synthases, Pyrazoles, Sulfonamides, Tumor Cells, Cultured, Eicosanoids, Cyclooxygenase Inhibitors, Gene Expression Profiling, Cell Proliferation

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