ArticleWorld journal of surgical oncology2012
Cyclooxygenase/lipoxygenase shunting lowers the anti-cancer effect of cyclooxygenase-2 inhibition in colorectal cancer cells.
Article in World journal of surgical oncology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
- Ketogenic diets attenuate cyclooxygenase and lipoxygenase gene expression in multiple sclerosis.EBioMedicine · 2018Trial
- The role of cyclooxygenase-2 in oxidative stress and inflammation: Implications for poultry health and production.Poultry science · 2026Review
- Radioiodination of Two Carborane-Based Dual Cyclooxygenase-2/5-Lipoxygenase Inhibitors and Their In Vitro and In Vivo Evaluation.Chembiochem : a European journal of chemical biology · 2026Article
- Whole-gene CRISPR/cas9 library screen revealed targeting STAT6 increased the sensitivity of liver cancer to celecoxib via inhibiting arachidonic acid shunting.Cell communication and signaling : CCS · 2025Article
- Innate Immune Reprogramming in Chronic Obstructive Pulmonary Disease: New Mechanisms for Old Questions.American journal of respiratory cell and molecular biology · 2023Article
- In Vitro Effects of Selective COX and LOX Inhibitors and Their Combinations with Antineoplastic Drugs in the Mouse Melanoma Cell Line B16F10.International journal of molecular sciences · 2021Article
- Onosma bracteata Wall. induces GEnvironmental science and pollution research international · 2021Article
- Resolution of eicosanoid/cytokine storm prevents carcinogen and inflammation-initiated hepatocellular cancer progression.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Druggable Sphingolipid Pathways: Experimental Models and Clinical Opportunities.Advances in experimental medicine and biology · 2020Review
- Dual Behavior of Long-Chain Fatty Acids and Their Cyclooxygenase/Lipoxygenase Metabolites on Human Intestinal Caco-2 Cell Growth.Frontiers in pharmacology · 2020Article
- Deletion of 5-Lipoxygenase in the Tumor Microenvironment Promotes Lung Cancer Progression and Metastasis through Regulating T Cell Recruitment.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Molecular targeted therapy for the treatment of gastric cancer.Journal of experimental & clinical cancer research : CR · 2016Review
- Radioprotective effect of mefenamic acid against radiation-induced genotoxicity in human lymphocytes.Radiation oncology journal · 2015Article
- Article
- Multiple drug resistance-associated protein 4 (MRP4), prostaglandin transporter (PGT), and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) as determinants of PGE2 levels in cancer.Prostaglandins & other lipid mediatorsReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundArachidonic acid metabolite, generated by cyclooxygenase (COX), is implicated in the colorectal cancer (CRC) pathogenesis. Inhibiting COX may therefore have anti-carcinogenic effects. Results from use of non-steroidal anti-inflammatory drugs inhibiting only COX have been conflicting. It has been postulated that this might result from the shunting of arachidonic acid metabolism to the 5-lipoxygenase (5-LOX) pathway. Cancer cell viability is promoted by 5-LOX through several mechanisms that are similar to those of cyclooxygenase-2 (COX-2). Expression of 5-LOX is upregulated in colorectal adenoma and cancer. The aim of this study was to investigate the shunting of arachidonic acid metabolism to the 5-LOX pathway by cyclooxygenase inhibition and to determine if this process antagonizes the anti-cancer effect in colorectal cancer cells.
methodsThree colorectal cancer cell lines (HCA7, HT-29 & LoVo) expressing 5-LOX and different levels of COX-2 expression were used. The effects of aspirin (a non-selective COX inhibitor) and rofecoxib (COX-2 selective) on prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) secretion were quantified by ELISA. Proliferation and viability were studied by quantifying double-stranded DNA (dsDNA) content and metabolic activity. Apoptosis was determined by annexin V and propidium iodide staining using confocal microscopy, and caspase-3/7 activity by fluorescent substrate assay.
resultsCOX inhibitors suppressed PGE2 production but enhanced LTB4 secretion in COX-2 expressing cell lines (P <0.001). The level of COX-2 expression in colorectal cancer cells did not significantly influence the anti-proliferative and pro-apoptotic effects of COX inhibitors due to the shunting mechanism.
conclusionsThis study provides evidence of shunting between COX and 5-LOX pathways in the presence of unilateral inhibition, and may explain the conflicting anti-carcinogenic effects reported with use of COX inhibitors.
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