Abstract
The results of clinical studies have shown that the chronic administration of aspirin, even at the lowdoses (75-100 mg daily) recommended for the prevention of cardiovascular disease, is associated with a reduction of cancer incidence and mortality, in particular colorectal cancer (CRC). The mechanism of action of aspirin as an antineoplastic agent remains controversial. However, data of clinical pharmacology and several features of the chemopreventive effect of aspirin, emerged from clinical trials, suggest that the antiplatelet effect of aspirin plays a central role in its anticancer effects. In addition to their contribution to tumor metastasis, platelets may play a role in the early phases of tumorigenesis. In response to lifestyle and environment factors, intestinal epithelial damage/ dysfunction may be associated with platelet activation, initially as a mechanism to repair the damage. However, if the platelet response is unconstrained, it may contribute to the development of chronic inflammation. Altogether these events lead to alter the normal functions of intestinal epithelial cells and may translate into cellular transformation through several mechanisms, including the overexpression of cyclooxygenase(COX)-2 and epidermal growth factor receptor (EGFR), which are considered early events in colorectal tumorigenesis. Thus, antiplatelet agents may play a role in the prevention of CRC by modifying epigenetic events involved in early phases of colorectal tumorigenesis. Finally, we carried out a critical review of the literature on off-target mechanisms of aspirin action as anticancer drug.
Keywords: Aspirin, coxibs, platelets, colorectal cancer, metastasis, cyclooxygenases, thromboxane A2, prostaglandin E2.
Current Pharmaceutical Design
Title:New Insights into the Mechanism of Action of Aspirin in the Prevention of Colorectal Neoplasia
Volume: 21 Issue: 35
Author(s): Luigia Di Francesco, Luilli Antonio López Contreras, Angela Sacco and Paola Patrignani
Affiliation:
Keywords: Aspirin, coxibs, platelets, colorectal cancer, metastasis, cyclooxygenases, thromboxane A2, prostaglandin E2.
Abstract: The results of clinical studies have shown that the chronic administration of aspirin, even at the lowdoses (75-100 mg daily) recommended for the prevention of cardiovascular disease, is associated with a reduction of cancer incidence and mortality, in particular colorectal cancer (CRC). The mechanism of action of aspirin as an antineoplastic agent remains controversial. However, data of clinical pharmacology and several features of the chemopreventive effect of aspirin, emerged from clinical trials, suggest that the antiplatelet effect of aspirin plays a central role in its anticancer effects. In addition to their contribution to tumor metastasis, platelets may play a role in the early phases of tumorigenesis. In response to lifestyle and environment factors, intestinal epithelial damage/ dysfunction may be associated with platelet activation, initially as a mechanism to repair the damage. However, if the platelet response is unconstrained, it may contribute to the development of chronic inflammation. Altogether these events lead to alter the normal functions of intestinal epithelial cells and may translate into cellular transformation through several mechanisms, including the overexpression of cyclooxygenase(COX)-2 and epidermal growth factor receptor (EGFR), which are considered early events in colorectal tumorigenesis. Thus, antiplatelet agents may play a role in the prevention of CRC by modifying epigenetic events involved in early phases of colorectal tumorigenesis. Finally, we carried out a critical review of the literature on off-target mechanisms of aspirin action as anticancer drug.
Export Options
About this article
Cite this article as:
Francesco Di Luigia, López Contreras Antonio Luilli, Sacco Angela and Patrignani Paola, New Insights into the Mechanism of Action of Aspirin in the Prevention of Colorectal Neoplasia, Current Pharmaceutical Design 2015; 21 (35) . https://dx.doi.org/10.2174/1381612821666150915110706
DOI https://dx.doi.org/10.2174/1381612821666150915110706 |
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
-
Imaging of Cyclooxygenase-2 (COX-2) Expression: Potential Use in Diagnosis and Drug Evaluation
Current Pharmaceutical Design Inhibition of Topoisomerase I by Anti-Cancer Drug Altered the Endometrial Cyclicity and Receptivity
Current Molecular Medicine Hedgehog Target Genes: Mechanisms of Carcinogenesis Induced by Aberrant Hedgehog Signaling Activation
Current Molecular Medicine Lectin-Immobilized Fluorescent Nanospheres for Targeting to Colorectal Cancer from a Physicochemical Perspective
Current Drug Discovery Technologies Therapeutic Targeting of the Endoplasmic Reticulum in Alzheimers Disease
Current Alzheimer Research Cytochromes P450 and Skin Cancer: Role of Local Endocrine Pathways
Anti-Cancer Agents in Medicinal Chemistry P-gp Inhibition-Based Strategies for Modulating Pharmacokinetics of Anticancer Drugs: An Update
Current Drug Metabolism Star Graphs of Protein Sequences and Proteome Mass Spectra in Cancer Prediction
Current Proteomics Editorial (Hot Topic: Vitamin D and Cancer: Current Evidence and Future Perspective)
Anti-Cancer Agents in Medicinal Chemistry Membrane Transporters as Determinants of the Pharmacology of Platinum Anticancer Drugs
Current Cancer Drug Targets The Urokinase Receptor Interactome
Current Pharmaceutical Design Developments in Synthesis of the Anti-inflammatory Drug, Celecoxib: A Review
Recent Patents on Inflammation & Allergy Drug Discovery Antiproliferative Activity of Olive Oil Phenolics against Human Melan oma Cells
Letters in Drug Design & Discovery The Dark Side of Stem Cells: Triggering Cancer Progression by Cell Fusion
Current Molecular Medicine Targeting Different Signaling Pathways with Antisense Oligonucleotides Combination for Cancer Therapy
Current Pharmaceutical Design Pharmacology and Therapeutic Applications of Enediyne Antitumor Antibiotics
Current Molecular Pharmacology Regulation of Inflammation: A Review of Recent Advances in Anti- Inflammatory Strategies
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Differential Action of Phytochemicals on Platelet Apoptosis: A Biological Overview
Current Medicinal Chemistry Molecular Targets for Nutritional Preemption of Cancer
Current Cancer Drug Targets microRNA Biogenesis Pathway as a Therapeutic Target for Human Disease and Cancer
Current Pharmaceutical Design