ArticlePloS one2014
HET0016, a selective inhibitor of 20-HETE synthesis, decreases pro-angiogenic factors and inhibits growth of triple negative breast cancer in mice.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 42 citations in OpenAlex.
- 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
- The Cytochrome CYP4 in Breast and Other Cancers.Biology · 2025Review
- Key regulator PNPLA8 drives phospholipid reprogramming induced proliferation and migration in triple-negative breast cancer.Breast cancer research : BCR · 2023Article
- Cytochrome P450: Implications for human breast cancer.Oncology letters · 2021Review
- Changes in the tumor microenvironment and outcome for TME-targeting therapy in glioblastoma: A pilot study.PloS one · 2021Article
- Targeting the eicosanoid pathway in hepatocellular carcinoma.American journal of cancer research · 2021Review
- Cytochrome P450 2U1 Is a Novel Independent Prognostic Biomarker in Breast Cancer Patients.Frontiers in oncology · 2020Article
- The Multifarious Link between Cytochrome P450s and Cancer.Oxidative medicine and cellular longevity · 2020Review
- Expression and Function of Eicosanoid-Producing Cytochrome P450 Enzymes in Solid Tumors.Frontiers in pharmacology · 2020Review
- Arachidonic Acid Metabolite as a Novel Therapeutic Target in Breast Cancer Metastasis.International journal of molecular sciences · 2017Review
- Vascular mimicry in glioblastoma following anti-angiogenic and anti-20-HETE therapies.Histology and histopathology · 2017Article
- CYP4A in tumor-associated macrophages promotes pre-metastatic niche formation and metastasis.Oncogene · 2017Article
- Vascular Mimicry: A Novel Neovascularization Mechanism Driving Anti-Angiogenic Therapy (AAT) Resistance in Glioblastoma.Translational oncology · 2017Review
- Role of 20-Hydroxyeicosatetraenoic Acid (20-HETE) in Androgen-Mediated Cell Viability in Prostate Cancer Cells.Hormones & cancer · 2017Article
- Shexiang Baoxin pills promotes angiogenesis in myocardial infarction rats via up-regulation of 20-HETE-mediated endothelial progenitor cells mobilization.Atherosclerosis · 2017Article
- Elevated 20-HETE impairs coronary collateral growth in metabolic syndrome via endothelial dysfunction.American journal of physiology. Heart and circulatory physiology · 2017Article
- Clinical Implications of 20-Hydroxyeicosatetraenoic Acid in the Kidney, Liver, Lung and Brain: An Emerging Therapeutic Target.Pharmaceutics · 2017Review
- Chemical synthesis and biological evaluation of ω-hydroxy polyunsaturated fatty acids.Bioorganic & medicinal chemistry letters · 2017Article
- Intravenous Formulation of HET0016 Decreased Human Glioblastoma Growth and Implicated Survival Benefit in Rat Xenograft Models.Scientific reports · 2017Article
- HET0016 decreases lung metastasis from breast cancer in immune-competent mouse model.PloS one · 2017Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
A selective inhibitor of 20-HETE synthesis, HET0016, has been reported to inhibit angiogenesis. 20-HETE has been known as a second mitogenic messenger of angiogenesis inducing growth factors. HET0016 effects were analyzed on MDA-MB-231 derived breast cancer in mouse and in vitro cell line. MDA-MB-231 tumor cells were implanted in animals' right flank and randomly assigned to early (1 and 2), starting treatments on day 0, or delayed groups (3 and 4) on day 8 after implantation of tumor. Animals received HET0016 (10 mg/kg) treatment via intraperitoneal injection for 5 days/week for either 3 or 4 weeks. Control group received vehicle treatment. Tumor sizes were measured on days 7, 14, 21, and 28 and the animals were euthanized on day 22 and 29. Proteins were extracted from the whole tumor and from cells treated with 10 µM HET0016 for 4 and 24 hrs. Protein array kits of 20 different cytokines/factors were used. ELISA was performed to observe the HIF-1α and MMP-2 protein expression. Other markers were confirmed by IHC. HET0016 significantly inhibited tumor growth in all treatment groups at all-time points compared to control (p<0.05). Tumor growth was completely inhibited on three of ten animals on early treatment group. Treatment groups showed significantly lower expression of pro-angiogenic factors compared to control at 21 days; however, there was no significant difference in HIF-1α expression after treatments. Similar results were found in vitro at 24 hrs of HET0016 treatment. After 28 days, significant increase of angiogenin, angiopoietin-1/2, EGF-R and IGF-1 pro-angiogenic factors were found (p<0.05) compared to control, as well as an higher intensity of all factors were found when compared to that of 21 day's data, suggesting a treatment resistance. HET0016 inhibited tumor growth by reducing expression of different set of pro-angiogenic factors; however, a resistance to treatment seemed to happen after 21 days.
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