Abstract
Arachidonic acids are converted to eicosanoid mediators by the distinct enzyme systems: cyclooxygenase, lipoxygenase and cytochrome P450 (CYP) monooxygenase pathways (ω/ω-1-hydroxylases and epoxygenases). CYP2J2, CYP2C8 and CYP2C9 are the predominant epoxygenase isoforms abundantly expressed in the endothelium, myocardium, and kidney in human. The primary epoxidation products by epoxygenases are four regioisomers of cisepoxyeicosatrienoic acids (EETs): 5,6-, 8,9-, 11,12-, and 14,15-EETs. Numerous studies demonstrated that the cardiovascular protective effects of CYP epoxygenases and EETs range from vasodilation, anti-hypertension, pro-angiogenesis, anti-atherosclerosis, and anti-inflammation to anti-injury caused by ischemia-reperfusion. The roles of arachidonic acids and its metabolites in cancer biology have recently attracted great attentions. However, CYP epoxygenase derived EETs and cancer has received little attention. It was demonstrated that CYP epoxygenases and EETs are significantly upregulated in human tumors and promote tumor progression and metastasis. Additionally, specific inhibitors of CYP2J2, derived from terfenadine, exhibit strong anti-tumor activity in vitro and in vivo. It is implicated that CYP2J2 may be a therapeutic target for treating human cancers.
Keywords: Arachidonic acid, cancer, cardiovascular disease, CYP epoxygenase, EET, signal pathways, therapy.
Current Topics in Medicinal Chemistry
Title:CYP Epoxygenase Derived EETs: From Cardiovascular Protection to Human Cancer Therapy
Volume: 13 Issue: 12
Author(s): Chen Chen and Dao Wen Wang
Affiliation:
Keywords: Arachidonic acid, cancer, cardiovascular disease, CYP epoxygenase, EET, signal pathways, therapy.
Abstract: Arachidonic acids are converted to eicosanoid mediators by the distinct enzyme systems: cyclooxygenase, lipoxygenase and cytochrome P450 (CYP) monooxygenase pathways (ω/ω-1-hydroxylases and epoxygenases). CYP2J2, CYP2C8 and CYP2C9 are the predominant epoxygenase isoforms abundantly expressed in the endothelium, myocardium, and kidney in human. The primary epoxidation products by epoxygenases are four regioisomers of cisepoxyeicosatrienoic acids (EETs): 5,6-, 8,9-, 11,12-, and 14,15-EETs. Numerous studies demonstrated that the cardiovascular protective effects of CYP epoxygenases and EETs range from vasodilation, anti-hypertension, pro-angiogenesis, anti-atherosclerosis, and anti-inflammation to anti-injury caused by ischemia-reperfusion. The roles of arachidonic acids and its metabolites in cancer biology have recently attracted great attentions. However, CYP epoxygenase derived EETs and cancer has received little attention. It was demonstrated that CYP epoxygenases and EETs are significantly upregulated in human tumors and promote tumor progression and metastasis. Additionally, specific inhibitors of CYP2J2, derived from terfenadine, exhibit strong anti-tumor activity in vitro and in vivo. It is implicated that CYP2J2 may be a therapeutic target for treating human cancers.
Export Options
About this article
Cite this article as:
Chen Chen and Wang Wen Dao, CYP Epoxygenase Derived EETs: From Cardiovascular Protection to Human Cancer Therapy, Current Topics in Medicinal Chemistry 2013; 13 (12) . https://dx.doi.org/10.2174/1568026611313120007
DOI https://dx.doi.org/10.2174/1568026611313120007 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Myocardial Energetics in Left Ventricular Hypertrophy
Current Cardiology Reviews Antidiabetic Drugs as Antihypertensives: New Data on the Horizon
Current Vascular Pharmacology Pathophysiology of Thrombosis and Potential Targeted Therapies in Antiphospholipid Syndrome
Current Vascular Pharmacology The Beneficial Hemodynamic Actions of SGLT-2 Inhibitors beyond the Management of Hyperglycemia
Current Medicinal Chemistry Metabolism in Patients with Rheumatoid Arthritis: Resting Energy Expenditure, Physical Activity and Diet-Induced Thermogenesis. Invited Review
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Melanotropins as Drugs for the Treatment of Obesity and Other Feeding Disorders: Potential and Problems
Current Topics in Medicinal Chemistry Vascular Endothelial Growth Factor Receptor as Target for Advanced Non-Small Cell Lung Cancer Therapy
Current Drug Targets Pathogenesis and Management of Hypertension after Kidney Transplantation
Current Hypertension Reviews The Akt-mTOR Pathway in Down’s Syndrome: The Potential Use of Rapamycin/Rapalogs for Treating Cognitive Deficits
CNS & Neurological Disorders - Drug Targets Analysis of Safety Outcomes in Chronic Hepatitis C Patients using Interferon-free Treatment: A Systematic Review of Case Reports
Current Drug Therapy Impact of Omega-3 and Trans Fatty Acids on Vascular Remodeling:Opposing Roles in Cardiovascular Health
Current Enzyme Inhibition Gynecomastia in Infants, Children, and Adolescents
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Cardiovascular Risk Prediction using JBS3 Tool: A Kerala based Study
Current Medical Imaging The Role of Trimetazidine After Acute Myocardial Infarction
Current Vascular Pharmacology AMI and Anabolic-Androgenic Steroids: Case Report with Systematic Review
Current Cardiology Reviews Nitric Oxide and its Antithrombotic Action in the Cardiovascular System
Current Drug Targets - Cardiovascular & Hematological Disorders Open Questions about Pulmonary Hypertension and Exercise Training: A Critical Review
Current Respiratory Medicine Reviews Meet Our Editorial Board Member
Current Hypertension Reviews A Review of the Relationships Between Endogenous Sex Steroids and Incident Ischemic Stroke and Coronary Heart Disease Events
Current Cardiology Reviews Targeting CSCs in Tumor Microenvironment: The Potential Role of ROS-Associated miRNAs in Tumor Aggressiveness
Current Stem Cell Research & Therapy