Abstract
The regular intake of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with decreased incidence of certain types of cancer particularly those with an inflammatory component. The protective effects of these drugs in colorectal cancer are particularly marked, with a 40-50% reduction in risk. Research in this area has focussed on understanding and optimising these cytoprotective effects. NSAIDs are believed to operate by inhibiting COX-2, an enzyme that appears to be involved in a number of cancer promoting processes. This hypothesis is consistent with the observation that the COX-2 selective inhibitors dramatically decrease tumour formation in human and animal studies. Surprisingly aspirin, which is selective for COX-1 over COX-2, and sulindac, which is an equipotent inhibitor of the COX isoenzymes, appear to have a similar anticancer profile to the COX-2 selective NSAIDs. A number of mechanisms have been proposed to explain the anomalous effects of aspirin. The first of these relates to the unique mode of action of aspirin, which acetylates the COX-2 enzyme and generates the cancer-suppressing 15R-hydroxyeicosatetraenoic acid at the site of a potential tumour. The alternative rationale relates to the metabolism of aspirin to salicylic acid, which has a cyclooxygenase independent anti-inflammatory mechanism, preventing the inflammatory response at the gene transcription level. A new generation of drugs could evolve from approaches to improving the therapeutic index of aspirin or by modifications to known therapies such as sulindac and celecoxib.
Keywords: colorectal cancer, aspirin, salicylic acid, cyclooxygenase, chemoprevention
Mini-Reviews in Medicinal Chemistry
Title: The Medicinal Chemistry Implications of the Anticancer Effects of Aspirin and Other NSAIDs
Volume: 3 Issue: 5
Author(s): P. S. Gardiner and J. F. Gilmer
Affiliation:
Keywords: colorectal cancer, aspirin, salicylic acid, cyclooxygenase, chemoprevention
Abstract: The regular intake of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with decreased incidence of certain types of cancer particularly those with an inflammatory component. The protective effects of these drugs in colorectal cancer are particularly marked, with a 40-50% reduction in risk. Research in this area has focussed on understanding and optimising these cytoprotective effects. NSAIDs are believed to operate by inhibiting COX-2, an enzyme that appears to be involved in a number of cancer promoting processes. This hypothesis is consistent with the observation that the COX-2 selective inhibitors dramatically decrease tumour formation in human and animal studies. Surprisingly aspirin, which is selective for COX-1 over COX-2, and sulindac, which is an equipotent inhibitor of the COX isoenzymes, appear to have a similar anticancer profile to the COX-2 selective NSAIDs. A number of mechanisms have been proposed to explain the anomalous effects of aspirin. The first of these relates to the unique mode of action of aspirin, which acetylates the COX-2 enzyme and generates the cancer-suppressing 15R-hydroxyeicosatetraenoic acid at the site of a potential tumour. The alternative rationale relates to the metabolism of aspirin to salicylic acid, which has a cyclooxygenase independent anti-inflammatory mechanism, preventing the inflammatory response at the gene transcription level. A new generation of drugs could evolve from approaches to improving the therapeutic index of aspirin or by modifications to known therapies such as sulindac and celecoxib.
Export Options
About this article
Cite this article as:
Gardiner S. P. and Gilmer F. J., The Medicinal Chemistry Implications of the Anticancer Effects of Aspirin and Other NSAIDs, Mini-Reviews in Medicinal Chemistry 2003; 3 (5) . https://dx.doi.org/10.2174/1389557033488033
DOI https://dx.doi.org/10.2174/1389557033488033 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...read more
Mitochondria as a Therapeutic Target in Metabolic Disorders
Mitochondria are the primary site of adenosine triphosphate (ATP) production in mammalian cells. Moreover, these organelles are an important source of reactive oxygen and nitrogen species in virtually any nucleated cell type. The modulation of a myriad of cellular signaling pathways depends on the mitochondrial physiology. Mitochondrial dysfunction is observed ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer?s, Parkinson?s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...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
Related Articles
-
Adjuvant and Neoadjuvant Therapy in Renal Cell Carcinoma
Current Clinical Pharmacology Developments in Synthesis of the Anti-inflammatory Drug, Celecoxib: A Review
Recent Patents on Inflammation & Allergy Drug Discovery BRAF Inhibitor Therapy for Melanoma, Thyroid and Colorectal Cancers: Development of Resistance and Future Prospects
Current Cancer Drug Targets In Silico Approach to Finding New Active Compounds from Histone Deacetylase (HDAC) Family
Current Pharmaceutical Design Advancements within Modern Machine Learning Methodology: Impacts and Prospects in Biomarker Discovery
Current Medicinal Chemistry Toward a Discipline of Pharmacoepigenomics
Current Pharmacogenomics Pharmacokinetic and Pharmacogenetic Markers of Irinotecan Toxicity
Current Medicinal Chemistry Advances in Nano Drugs for Cancer Chemotherapy
Current Cancer Drug Targets Namitecan: a Hydrophilic Camptothecin with a Promising Preclinical Profile
Current Medicinal Chemistry Treatment of Colorectal Liver Metastases: A Review
Reviews on Recent Clinical Trials Ribosomal Proteins and Colorectal Cancer
Current Genomics Analgesia in PACU: Nonsteroidal Anti-Inflammatory Drugs
Current Drug Targets Cancer Stem Cells: The ‘Achilles Heel’ of Chemo-Resistant Tumors
Recent Patents on Anti-Cancer Drug Discovery Role of α6β4 Integrin in Cell Motility, Invasion and Metastasis of Mammary Tumors
Current Protein & Peptide Science Metabolic and Amino Acid Alterations of the Tumor Microenvironment
Current Medicinal Chemistry Biomedical Applications of Natural Polymers for Drug Delivery
Current Organic Chemistry Clinical Use of Therapies Targeting Tumor Vasculature and Stroma
Current Cancer Drug Targets Targeting Synthetic Lethality in DNA Damage Repair Pathways as an Anti-Cancer Strategy
Current Drug Targets Derivatives of Procaspase-Activating Compound 1 (PAC-1) and their Anticancer Activities
Current Medicinal Chemistry Sorafenib (BAY 43-9006): Review of Clinical Development
Current Clinical Pharmacology