ArticleCancer chemotherapy and pharmacology2011
Cytochrome P450 ω-hydroxylase promotes angiogenesis and metastasis by upregulation of VEGF and MMP-9 in non-small cell lung cancer.
Article in Cancer chemotherapy and pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 87 citations in OpenAlex.
- Article
- On the interface of fatty acid metabolism: A crosstalk between fatty acid ω-hydroxylase CYP4F11 and fatty acid desaturase 2 in non-small cell lung cancer.Drug metabolism and disposition: the biological fate of chemicals · 2026Article
- Functional studies on the cytochrome P450 splice variants CYP4F3A and CYP4F3B unveil the basis for their distinct physiological functions.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Immunoregulatory mechanisms of the arachidonic acid pathway in cancer.FEBS letters · 2025Review
- Recent Insights into the Angioregulatory Role of Long Non-coding RNAs and Circular RNAs in Gliomas: From Signaling Pathways to Clinical Aspects.Current medicinal chemistry · 2025Review
- Metabolic Targets in CRC: The Emerging Role of Cytochrome P450 Inhibitors.Current pharmaceutical design · 2025Review
- Establishment of a neutrophil extracellular trap-related prognostic signature for colorectal cancer liver metastasis and expression validation of CYP4F3.Clinical and experimental medicine · 2024Article
- Arachidonic acid metabolism as a therapeutic target in AKI-to-CKD transition.Frontiers in pharmacology · 2024Review
- Cytochrome P450 27C1 Level Dictates Lung Cancer Tumorigenicity and Sensitivity towards Multiple Anticancer Agents and Its Potential Interplay with the IGF-1R/Akt/p53 Signaling Pathway.International journal of molecular sciences · 2022Article
- Omega-6 Polyunsaturated Fatty Acids Enhance Tumor Aggressiveness in Experimental Lung Cancer Model: Important Role of Oxylipins.International journal of molecular sciences · 2022Article
- Alteration in Plasma Metabolome in High-Fat Diet-Fed Monocyte Chemotactic Protein-1 Knockout Mice Bearing Pulmonary Metastases of Lewis Lung Carcinoma.Nutrition and metabolic insights · 2022Article
- Metabolism pathways of arachidonic acids: mechanisms and potential therapeutic targets.Signal transduction and targeted therapy · 2021Review
- 20-HETE synthesis inhibition attenuates traumatic brain injury-induced mitochondrial dysfunction and neuronal apoptosis via the SIRT1/PGC-1α pathway: A translational study.Cell proliferation · 2021Article
- Comparative Metabolomics Reveals the Microenvironment of Common T-Helper Cells and Differential Immune Cells Linked to Unique Periapical Lesions.Frontiers in immunology · 2021Article
- The Functions of Cytochrome P450 ω-hydroxylases and the Associated Eicosanoids in Inflammation-Related Diseases.Frontiers in pharmacology · 2021Review
- Increased pro-MMP9 plasma levels are associated with neovascular age-related macular degeneration and with the risk allele of rs142450006 nearMolecular vision · 2021Article
- CYP4F2 and CYP3A5 gene polymorphisms and lung cancer in Chinese Han population.Clinical and experimental medicine · 2020Article
- GPR75 receptor mediates 20-HETE-signaling and metastatic features of androgen-insensitive prostate cancer cells.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2020Article
- Expression and Function of Eicosanoid-Producing Cytochrome P450 Enzymes in Solid Tumors.Frontiers in pharmacology · 2020Review
- Pleiotropic Functions of Cytochrome P450 Monooxygenase-Derived Eicosanoids in Cancer.Frontiers in pharmacology · 2020Review
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
Abstract
purposeCytochrome P450 (CYP) ω-hydroxylase, mainly consisting of CYP4A and CYP4F, converts arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE) that induces angiogenic responses in vivo and in vitro. The present study examined the role of CYP ω-hydroxylase in angiogenesis and metastasis of human non-small cell lung cancer (NSCLC).
methodsThe effect of WIT003, a stable 20-HETE analog, on invasion was evaluated using a modified Boyden chamber in three NSCLC cell lines. A549 cells were transfected with CYP4A11 expression vector or exposed to CYP ω-hydroxylase inhibitor (HET0016) or 20-HETE antagonist (WIT002), and then ω-hydroxylation activity toward arachidonic acid and the levels of matrix metalloproteinases (MMPs) and VEGF were detected. The in vivo effects of CYP ω-hydroxylase were tested in established tumor xenografts and an experimental metastasis model in athymic mice.
resultsAddition of WIT003 or overexpression of CYP4A11 with an associated increase in 20-HETE production significantly induced invasion and expression of VEGF and MMP-9. Treatment of A549 cells with HET0016 or WIT002 inhibited invasion with reduction in VEGF and MMP-9. The PI3 K or ERK inhibitors also attenuated expression of VEGF and MMP-9. Compared with control, CYP4A11 transfection significantly increased tumor weight, microvessel density (MVD), and lung metastasis by 2.5-fold, 2-fold, and 3-fold, respectively. In contrast, WIT002 or HET0016 decreased tumor volume, MVD, and spontaneous pulmonary metastasis occurrences.
conclusionCYP ω-hydroxylase promotes tumor angiogenesis and metastasis by upregulation of VEGF and MMP-9 via PI3 K and ERK1/2 signaling in human NSCLC cells.
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