Abstract
Multidrug resistance (MDR) of cancer cells to cytostatic agents is the major obstacle for the succesfull chemotherapy. One of the causes of the development of cellular resistance to a wide variety of drugs is the elevated expression of membrane transporter proteins such as members of ATP binding cassette (ABC) protein superfamily. Expression of the ABC transporter MDR1, also termed P-glycoprotein (P-gp), seems to correlate with drug resistance of tumors to chemotherapy. Cyclooxygenase-2, an inducible isoform of enzyme, responsible for generation of prostaglandins from arachidonic acid, is constitutively expressed in a number of cancer cells. Anti-cancer potency of cyclooxygenase inhibitors is established, but the mechanism of Cox-2-dependent potentiation of tumor growth is a subject of intense discussion. Here we focus on the discussion of potential link between Cox-2 expression and development of multidrug resistance phenotype. Our observation, that enforced expression of Cox-2 causes enhancement in MDR1 expression and functional activity suggests the existence of causal link between Cox-2 activity and MDR1 expression. The use of Cox-2 inhibitors to decrease function of MDR1 may enhance accumulation of chemotherapy agents and decrease resistance of tumors to chemotherapeutic drugs.
Keywords: cyclooxygenase, prostaglandins, P-glycoprotein, multidrug resistance, mdr1, renal mesangial, apoptosis, chemotherapeutic agents
Current Pharmaceutical Design
Title: Cyclooxygenase-2: Potential Role in Regulation of Drug Efflux and Multidrug Resistance Phenotype
Volume: 10 Issue: 6
Author(s): A. Sorokin
Affiliation:
Keywords: cyclooxygenase, prostaglandins, P-glycoprotein, multidrug resistance, mdr1, renal mesangial, apoptosis, chemotherapeutic agents
Abstract: Multidrug resistance (MDR) of cancer cells to cytostatic agents is the major obstacle for the succesfull chemotherapy. One of the causes of the development of cellular resistance to a wide variety of drugs is the elevated expression of membrane transporter proteins such as members of ATP binding cassette (ABC) protein superfamily. Expression of the ABC transporter MDR1, also termed P-glycoprotein (P-gp), seems to correlate with drug resistance of tumors to chemotherapy. Cyclooxygenase-2, an inducible isoform of enzyme, responsible for generation of prostaglandins from arachidonic acid, is constitutively expressed in a number of cancer cells. Anti-cancer potency of cyclooxygenase inhibitors is established, but the mechanism of Cox-2-dependent potentiation of tumor growth is a subject of intense discussion. Here we focus on the discussion of potential link between Cox-2 expression and development of multidrug resistance phenotype. Our observation, that enforced expression of Cox-2 causes enhancement in MDR1 expression and functional activity suggests the existence of causal link between Cox-2 activity and MDR1 expression. The use of Cox-2 inhibitors to decrease function of MDR1 may enhance accumulation of chemotherapy agents and decrease resistance of tumors to chemotherapeutic drugs.
Export Options
About this article
Cite this article as:
Sorokin A., Cyclooxygenase-2: Potential Role in Regulation of Drug Efflux and Multidrug Resistance Phenotype, Current Pharmaceutical Design 2004; 10 (6) . https://dx.doi.org/10.2174/1381612043453117
DOI https://dx.doi.org/10.2174/1381612043453117 |
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
-
Anthracycline Cardiotoxicity: Prevalence, Pathogenesis and Treatment
Current Cardiology Reviews Significant Metabolites and Outlier-Robust Classifier Identification for Breast Cancer Prediction
Current Metabolomics Natural Products as Farnesoid X Receptor (FXR) Agonists: Their Interactions with FXR Ligand Binding Region
Mini-Reviews in Organic Chemistry Adrenomedullin Expression in Alzheimer's Brain
Current Alzheimer Research The First Organometallic Selective Estrogen Receptor Modulators (SERMs) and Their Relevance to Breast Cancer
Current Medicinal Chemistry Lipid Based Nanoparticles as Inherent Reversing Agents of Multidrug Resistance in Cancer
Current Pharmaceutical Design Resveratrol Inhibits the Epithelial-Mesenchymal Transition of Pancreatic Cancer Cells Via Suppression of the PI-3K/Akt/NF-κB Pathway
Current Medicinal Chemistry Self-Assembled Micelles of Amphiphilic PEGylated Drugs for Cancer Treatment
Current Drug Targets Targeting Endothelial Progenitor Cells in Cancer as a Novel Biomarker and Anti-Angiogenic Therapy
Current Stem Cell Research & Therapy The Effect of Natural Soluble Polysaccharides on the Type 2 Diabetes through Modulating Gut Microbiota: A Review
Current Medicinal Chemistry Modulation and Absorption of Xenobiotics: The Synergistic Role of CYP450 and P-gp Activities in Cancer and Neurodegenerative Disorders
Current Drug Metabolism Macrocyclic Lactones and Cellular Transport-Related Drug Interactions: A Perspective from In Vitro Assays to Nematode Control in the Field
Current Pharmaceutical Biotechnology Antiangiogenic Effect of Isomalyngamide A Riboside CY01 in Breast Cancer Cells <i>via</i> Inhibition of Migration, Tube Formation and pVEGFR2/pAKT Signals
Anti-Cancer Agents in Medicinal Chemistry Role of the Receptor Tyrosine Kinase Axl and its Targeting in Cancer Cells
Current Medicinal Chemistry Current and Future Applications of Probiotics
Current Nutrition & Food Science The Tumor Suppressor Role of the Ras Association Domain Family 10
Anti-Cancer Agents in Medicinal Chemistry Functional Non-Synonymous Polymorphisms Prediction Methods: Current Approaches and Future Developments
Current Medicinal Chemistry Potential Cancer Gene Therapy by Baculoviral Transduction
Current Gene Therapy Role of PARP Inhibitors in Cancer Biology and Therapy
Current Medicinal Chemistry Beyond Trastuzumab: Overcoming Resistance to Targeted HER-2 Therapy in Breast Cancer
Current Cancer Drug Targets