ArticleOncoTargets and therapy2018
Zileuton suppresses cholangiocarcinoma cell proliferation and migration through inhibition of the Akt signaling pathway.
Article in OncoTargets and therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Molecular Targets and Signaling Pathways in Cholangiocarcinoma: A Systematic Review.Asian Pacific journal of cancer prevention : APJCP · 2023Pooled it
- Zileuton protects pancreatic stellate cells from oxidative stress and ferroptosis by modulating the Nrf2 pathway and mitochondrial activity.Journal of physiology and biochemistry · 2026Article
- Reprogramming of fatty acid metabolism: a hidden force regulating the occurrence and progression of cholangiocarcinoma.Cell death discovery · 2025Review
- Elucidating the role of S100A10 in CD8Cell death & disease · 2024Article
- Potential of Anti-Leukotriene Drugs as New Therapeutic Agents for Inhibiting Cholangiocarcinoma Progression.Molecules (Basel, Switzerland) · 2024Article
- ALOX5 acts as a key role in regulating the immune microenvironment in intrahepatic cholangiocarcinoma, recruiting tumor-associated macrophages through PI3K pathway.Journal of translational medicine · 2023Article
- Detection of Ferroptosis by Immunohistochemistry and Immunofluorescence.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Article
- Regorafenib inhibits epithelial-mesenchymal transition and suppresses cholangiocarcinoma metastasis via YAP1-AREG axis.Cell death & disease · 2022Article
- Zileuton inhibits arachidonate-5-lipoxygenase to exert antitumor effects in preclinical cervical cancer models.Cancer chemotherapy and pharmacology · 2021Article
- Montelukast potentiates the antiinflammatory effect of NSAIDs in the rat paw formalin model and simultaneously minimizes the risk of gastric damage.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2021Article
- ALOX5-5-HETE promotes gastric cancer growth and alleviates chemotherapy toxicity via MEK/ERK activation.Cancer medicine · 2021Article
- Lipoxins and Resolvins in Patients With Pancreatic Cancer: A Preliminary Report.Frontiers in oncology · 2021Article
- Eicosapentaenoic acid's metabolism of 15-LOX-1 promotes the expression of miR-101 thus inhibits Cox2 pathway in colon cancer.OncoTargets and therapy · 2020Article
- Article
- A new treatment for severe pulmonary arterial hypertension based on an old idea: inhibition of 5-lipoxygenase.Pulmonary circulationArticle
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundInflammatory lipid mediators play an important role in several cancer types. Leukotrienes (LTs), pro-inflammatory lipid mediators, are involved in chronic inflammation and cancer progression. They are derived from arachidonic acid by 5-lipoxygenase (5-LOX) activity. On the other hand, 15-lipoxygenase (15-LOX-1) converts LTs into lipoxins (LXs), pro-resolving lipid mediators. LXs are involved in the attenuation of inflammation and cancer development. PURPOSE: We aimed to investigate the lipid mediator pathways, especially the LTs and LXs pathways, by studying 5-LOX and 15-LOX-1 expression in human cholangiocarcinoma (CCA) tissue. We also investigated the efficiency of zileuton (5-LOX inhibitor) treatment and BML-111 (LXA4 analog) addition on CCA cell lines properties. PATIENTS AND
methodsThe expression of 5-LOX and 15-LOX-1 in fifty human cholangiocarcinoma (CCA) tissue was analyzed using immunohistochemical staining. In addition, the effect of zileuton and BML-111 on CCA cell growth and migration was demonstrated using a cell viability assay and wound-healing assay, respectively. Furthermore, the molecular mechanism by which zileuton inhibits CCA cell migration was revealed using immunofluorescent staining and western blot analysis, respectively.
resultsWe demonstrate that the upregulation of 5-LOX is significantly correlated with CCA recurrent status. A positive 15-LOX-1 signal was significantly associated with a longer survival time in CCA patients. We found that co-expression of 5-LOX and 15-LOX-1 resulted in a relatively good prognosis in CCA patients. In addition, zileuton could inhibit CCA cell migration as well as BML-111. Interestingly, zileuton treatment not only downregulated 5-LOX, but also upregulated 15-LOX-1, together with reversing the epithelial-mesenchymal transition to mesenchymal-epithelial transition phenotype as observed in EMT marker western blot.
conclusionThese findings suggest that 5-LOX and 15-LOX-1 play a key role in CCA and may serve as targets for CCA therapy.
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