Abstract
Metabolites of arachidonic acid participate in normal growth responses and in aberrant cellular growth and proliferation, including carcinogenesis. The key step in the conversion of free arachidonic acid to prostaglandins is catalyzed by the cyclooxygenase enzyme (COX). There are two COX enzymes, COX-1 and COX-2. COX-1 is expressed constitutively and is part of normal cell metabolic functions. COX-2, on the other hand, is induced and expressed in neoplastic growths. The connection between COX expression and carcinogenesis was first implicated in studies that demonstrated the efficacy of aspirin and non-steroidal anti-inflammatory drugs to reduce the relative risk of colon cancer and also promote tumor regression in both humans and animal models of colon cancer. Investigation of the molecular basis of these observations showed that high levels of COX-2 protein were present in both human and animal colorectal tumors. A variety of evidence gathered from epidemiological, whole animal, and cellular studies indicate that unregulated COX-2 expression is a rate-limiting step in tumorigenesis and also that the loss of regulation occurs early in carcinogenesis. The interest in the COX-2 enzyme is that specific inhibition of COX-2 could theoretically avoid the gastrointestinal and other complications observed with the use of nonspecific COX inhibitors (most NSAIDs) or COX-1 inhibitors. The mechanisms by which COX-2 inhibitors lead to decreased colon carcinogenesis are not fully understood but they involve an increase not only in COX-2 dependent but also in COX-2 independent mechanisms.
Keywords: colorectal cancer, cyclooxygenase, prostaglandins, nsaids
Current Pharmaceutical Design
Title: COX-2 and Colorectal Cancer
Volume: 9 Issue: 27
Author(s): A. Ferrandez, S. Prescott and R. W. Burt
Affiliation:
Keywords: colorectal cancer, cyclooxygenase, prostaglandins, nsaids
Abstract: Metabolites of arachidonic acid participate in normal growth responses and in aberrant cellular growth and proliferation, including carcinogenesis. The key step in the conversion of free arachidonic acid to prostaglandins is catalyzed by the cyclooxygenase enzyme (COX). There are two COX enzymes, COX-1 and COX-2. COX-1 is expressed constitutively and is part of normal cell metabolic functions. COX-2, on the other hand, is induced and expressed in neoplastic growths. The connection between COX expression and carcinogenesis was first implicated in studies that demonstrated the efficacy of aspirin and non-steroidal anti-inflammatory drugs to reduce the relative risk of colon cancer and also promote tumor regression in both humans and animal models of colon cancer. Investigation of the molecular basis of these observations showed that high levels of COX-2 protein were present in both human and animal colorectal tumors. A variety of evidence gathered from epidemiological, whole animal, and cellular studies indicate that unregulated COX-2 expression is a rate-limiting step in tumorigenesis and also that the loss of regulation occurs early in carcinogenesis. The interest in the COX-2 enzyme is that specific inhibition of COX-2 could theoretically avoid the gastrointestinal and other complications observed with the use of nonspecific COX inhibitors (most NSAIDs) or COX-1 inhibitors. The mechanisms by which COX-2 inhibitors lead to decreased colon carcinogenesis are not fully understood but they involve an increase not only in COX-2 dependent but also in COX-2 independent mechanisms.
Export Options
About this article
Cite this article as:
Ferrandez A., Prescott S. and Burt W. R., COX-2 and Colorectal Cancer, Current Pharmaceutical Design 2003; 9 (27) . https://dx.doi.org/10.2174/1381612033454036
DOI https://dx.doi.org/10.2174/1381612033454036 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
microRNA as Biomarkers and Regulator of Cardiovascular Development and Disease
Current Pharmaceutical Design Pharmacological Intervention at CCR1 and CCR5 as an Approach for Cancer: Help or Hindrance
Current Topics in Medicinal Chemistry Genetic Surgery - A Right Strategy to Attack Cancer
Current Gene Therapy Dual Targeting of Glioma U251 Cells with Nanoparticles Prevents Tumor Angiogenesis and Inhibits Tumor Growth
Current Neurovascular Research Forms of Iron Binding in the Cells and the Chemical Features of Chelation Therapy
Mini-Reviews in Medicinal Chemistry Recent Advances in Copper Radiopharmaceuticals
Current Radiopharmaceuticals Vitamin D and Lung Cancer
Current Respiratory Medicine Reviews Fibrates in the Chemical Action of Daunorubicin
Current Cancer Drug Targets Targeting Angiogenesis for Treatment of NSCLC Brain Metastases
Current Cancer Drug Targets Antioxidant Supplements, Genetics and Chemotherapy Outcomes
Current Cancer Therapy Reviews Geriatric Evaluation of Oncological Elderly Patients
Anti-Cancer Agents in Medicinal Chemistry Suppression of Cancer Invasiveness by Dietary Compounds
Mini-Reviews in Medicinal Chemistry Natural-based Hydrogels: A Journey from Simple to Smart Networks for Medical Examination
Current Medicinal Chemistry Biomarkers to Assess the Targeting of DNA Repair Pathways to Augment Tumor Response to Therapy
Current Molecular Medicine VEGF in Tumor Progression and Targeted Therapy
Current Cancer Drug Targets Targeting Mammalian Target of Rapamycin: Prospects for the Treatment of Inflammatory Bowel Diseases
Current Medicinal Chemistry Current Approaches to Glycoprotein Analysis
Protein & Peptide Letters Nucleosides, a Valuable Chemical Marker for Quality Control in Traditional Chinese Medicine Cordyceps
Recent Patents on Biotechnology ErbB4 and its Isoforms: Patentable Drug Targets?
Recent Patents on DNA & Gene Sequences Mesalamine for Inflammatory Bowel Disease: Recent Reappraisals
Inflammation & Allergy - Drug Targets (Discontinued)