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
-
Phytometabolites Targeting the Warburg Effect in Cancer Cells: A Mechanistic Review
Current Drug Targets Activation of LINE-1 Retrotransposon Increases the Risk of Epithelial-Mesenchymal Transition and Metastasis in Epithelial Cancer
Current Molecular Medicine Gene Expression Signatures of Lymph Node Metastasis in Oral Cancer: Molecular Characteristics and Clinical Significances
Current Cancer Therapy Reviews Effects of PHA-665752 and Cetuximab Combination Treatment on In Vitro and Murine Xenograft Growth of Human Colorectal Cancer Cells with KRAS or BRAF Mutations
Current Cancer Drug Targets Ectodomain Shedding and Regulated Intracellular Proteolysis in the Central Nervous System
Central Nervous System Agents in Medicinal Chemistry Anti-Angiogenic Treatment for Exudative Age-Related Macular Degeneration: New Strategies are Underway
Current Angiogenesis (Discontinued) Metal Containing Cytostatics and Their Interaction with Cellular Thiol Compounds Causing Chemoresistance
Anti-Cancer Agents in Medicinal Chemistry 4-Hydroxynonenal in the Pathogenesis and Progression of Human Diseases
Current Medicinal Chemistry Cytochrome P450 2W1 (CYP2W1) in Colorectal Cancers
Current Cancer Drug Targets Melatonin Induces Apoptosis and Inhibits the Proliferation of Cancer Cells via Reactive Oxygen Species-mediated MAPK and mTOR Pathways
Clinical Cancer Drugs Mucosal Healing in Crohn’s Disease: Relevance for Clinical Outcomes
Current Drug Targets Role of Rap2 and its Downstream Effectors in Tumorigenesis
Anti-Cancer Agents in Medicinal Chemistry Differential Expression of miR-20a and miR-145 in Colorectal Tumors as Potential Location-specific miRNAs
MicroRNA Resveratrol Targets in Inflammation
Endocrine, Metabolic & Immune Disorders - Drug Targets Development of Cancer Vaccine Targeting WT1 Product which is Expressed in Various Kinds of Malignant Neoplasms
Medicinal Chemistry Reviews - Online (Discontinued) Mechanisms of Intrinsic and Acquired Resistance to EGFR Inhibitors
Current Cancer Therapy Reviews An Emerging Strategy for Cancer Treatment Targeting Aberrant Glycogen Synthase Kinase 3β
Anti-Cancer Agents in Medicinal Chemistry Active Subnetwork GA: A Two Stage Genetic Algorithm Approach to Active Subnetwork Search
Current Bioinformatics Potential Application of Gene Therapy to X-Linked Agammaglobulinemia
Current Gene Therapy Lysophospholipids: Synthesis and Biological Aspects
Current Organic Chemistry