ArticleCancer chemotherapy and pharmacology2021
Zileuton inhibits arachidonate-5-lipoxygenase to exert antitumor effects in preclinical cervical cancer models.
Article in Cancer chemotherapy and pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Zileuton protects pancreatic stellate cells from oxidative stress and ferroptosis by modulating the Nrf2 pathway and mitochondrial activity.Journal of physiology and biochemistry · 2026Article
- 7-O-methylpunctatin is a potential inhibitor of human arachidonate 5-lipoxygenase: molecular and structural insights into anti-atherosclerosis therapeutics.Molecular diversity · 2026Article
- 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
- Bioactive compounds in European ferns: inhibition of pro-inflammatory enzymes and cytotoxic effects on cancer cells.BMC complementary medicine and therapies · 2026Article
- Irisin regulates lipid metabolism and ferroptosis in ovarian cancer cells by modulating the ALOX5-5-HETE-PD-L1 axis.Scientific reports · 2026Article
- Spatial Transcriptomics Reveals Distinct Architectures but Shared Vulnerabilities in Primary and Metastatic Liver Tumors.Cancers · 2025Article
- Identification and characterization of salivary immune complex antigens in oral cancer.Clinical oral investigations · 2025Article
- Ferroptosis as a Form of Cell Death-Medical Importance and Pharmacological Implications.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Targeting circulating tumor cell‒neutrophil interactions: nanoengineered strategies for inhibiting cancer metastasis.Journal of nanobiotechnology · 2025Review
- Significance of non-steroidal anti-inflammatory drugs in the prevention and treatment of cervical cancer.Heliyon · 2025Review
- Investigation of Antimicrobial and Anti-Inflammatory Efficacy of Newly Synthesized Pyrogallol-Coumarin Hybrids:Pharmaceutics · 2024Article
- The role of human 5-Lipoxygenase (5-LO) in carcinogenesis - a question of canonical and non-canonical functions.Oncogene · 2024Review
- 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
- Three-dimensional growth reveals fine-tuning of 5-lipoxygenase by proliferative pathways in cancer.Life science alliance · 2023Article
- Knock-out of 5-lipoxygenase in overexpressing tumor cells-consequences on gene expression and cellular function.Cancer gene therapy · 2023Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundInhibitors of arachidonate lipoxygenase 5 (ALOX5) exhibit anticancer activity. Zileuton is an FDA-approved drug for treating asthma and an ALOX5 inhibitor. This study evaluated the efficacy of zileuton in cervical cancer, determined the molecular mechanism of action, and assessed ALOX5 expression in cervical cancer patients.
methodsThe effects of zileuton were evaluated using cervical cancer cell lines and xenograft mouse models. Loss-of-function analysis of ALOX5 was performed using siRNA. The levels of ALOX5 and 5-HETE were determined using immunohistochemistry and ELISA.
resultsZileuton resulted in cell proliferation inhibition and apoptosis induction in a dose-dependent manner, regardless of cellular origin or HPV infection. In two independent cervical cancer xenograft mouse models, zileuton at nontoxic doses significantly prevented tumor formation and decreased tumor growth. Zileuton acts on cervical cancer cells by inhibiting the ALOX5-5-HETE axis. Of note, ALOX5-5-HETE was significantly upregulated in cervical cancer compared with normal tissue. Inhibition of ALOX5 via the siRNA approach mimics the inhibitory effects of zileuton and confirms the roles of ALOX5 in cervical cancer.
conclusionsOur work demonstrates that the ALOX5-5-HETE axis is activated in cervical cancer, with important roles in growth and survival, and this can be therapeutically targeted by zileuton. Our findings also provide preclinical evidence to assess the efficacy of zileuton in cervical cancer in clinical settings.
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