Abstract
Cancer cells are permanently being selected for survival and proliferation. During this process, tumor cells often co-opt basic physiological mechanisms to protect themselves from toxic chemotherapy. One of these mechanisms is the overexpression of ATP-binding cassette (ABC) drug efflux pumps leading to multidrug resistance (MDR) of cancer cells through an increase of drug efflux. In the past 20 years, many efforts were done to circumvent MDR through the inhibition of ABC transporters. A number of inhibitors of these transporters were found but are rarely specific or rationally developed. Beside this approach, a new therapeutic strategy towards eradicating drug resistant tumor cells has recently emerged from the observation that cancer cells expressing a high level of these pumps show an unexpected hypersensitivity, called collateral sensitivity (CS) to a selected subset of chemical compounds. In this review, we target the multidrug resistance protein 1 (MRP1) and after a non-exhaustively highlighting of some of the most exemplary inhibitors of MRP1 and modulators of its expression, we focus on CS agents specifically targeting MRP1 which becomes, when overexpressed, the so called "Achilles' heel" of multidrug resistant cancer cells. We discuss the link between the prominent role of glutathione translocation and related redox balance of the cell and the CS induced by certain types of compounds. The latter are discussed according to their chemical class, and perspectives in their development for successful eradication of resistant cancer are proposed.
Keywords: ABCC1/MRP1, multidrug resistance protein 1, glutathione, collateral sensitivity, drug design, flavonoids, molecular models, multidrug resistance, Quantitative Structure-Activity Relationships.
Current Medicinal Chemistry
Title:MRP1-dependent Collateral Sensitivity of Multidrug-resistant Cancer Cells: Identifying Selective Modulators Inducing Cellular Glutathione Depletion
Volume: 24 Issue: 12
Author(s): Doriane Lorendeau, Lauriane Dury, Rachad Nasr, Ahcene Boumendjel, Elisabetta Teodori, Michael Gutschow, Pierre Falson, Attilio Di Pietro and Helene Baubichon-Cortay*
Affiliation:
- Drug Resistance and Membrane Proteins, UMR 5086 CNRS/Université Lyon 1, Molecular Microbiology and Structural Biochemistry, IBCP, 7 passage du Vercors, 69367 Lyon,France
Keywords: ABCC1/MRP1, multidrug resistance protein 1, glutathione, collateral sensitivity, drug design, flavonoids, molecular models, multidrug resistance, Quantitative Structure-Activity Relationships.
Abstract: Cancer cells are permanently being selected for survival and proliferation. During this process, tumor cells often co-opt basic physiological mechanisms to protect themselves from toxic chemotherapy. One of these mechanisms is the overexpression of ATP-binding cassette (ABC) drug efflux pumps leading to multidrug resistance (MDR) of cancer cells through an increase of drug efflux. In the past 20 years, many efforts were done to circumvent MDR through the inhibition of ABC transporters. A number of inhibitors of these transporters were found but are rarely specific or rationally developed. Beside this approach, a new therapeutic strategy towards eradicating drug resistant tumor cells has recently emerged from the observation that cancer cells expressing a high level of these pumps show an unexpected hypersensitivity, called collateral sensitivity (CS) to a selected subset of chemical compounds. In this review, we target the multidrug resistance protein 1 (MRP1) and after a non-exhaustively highlighting of some of the most exemplary inhibitors of MRP1 and modulators of its expression, we focus on CS agents specifically targeting MRP1 which becomes, when overexpressed, the so called "Achilles' heel" of multidrug resistant cancer cells. We discuss the link between the prominent role of glutathione translocation and related redox balance of the cell and the CS induced by certain types of compounds. The latter are discussed according to their chemical class, and perspectives in their development for successful eradication of resistant cancer are proposed.
Export Options
About this article
Cite this article as:
Lorendeau Doriane, Dury Lauriane, Nasr Rachad, Boumendjel Ahcene, Teodori Elisabetta, Gutschow Michael, Falson Pierre, Di Pietro Attilio and Baubichon-Cortay Helene*, MRP1-dependent Collateral Sensitivity of Multidrug-resistant Cancer Cells: Identifying Selective Modulators Inducing Cellular Glutathione Depletion, Current Medicinal Chemistry 2017; 24 (12) . https://dx.doi.org/10.2174/0929867324666161118130238
DOI https://dx.doi.org/10.2174/0929867324666161118130238 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
-
Antioxidant Agents in Alzheimers Disease
Central Nervous System Agents in Medicinal Chemistry Radiofrequency Radiation and Human Triiodothronine Hormone: Immunoenzymometric Assay
Recent Patents on Biomarkers L-Type Voltage-Dependent Calcium Channels As Therapeutic Targets for Neurodegenerative Diseases
Current Medicinal Chemistry Serotonergic 5-HT<sub>6</sub> Receptor Antagonists: Heterocyclic Chemistry and Potential Therapeutic Significance
Current Topics in Medicinal Chemistry Anionic Host Defence Peptides from the Plant Kingdom: Their Anticancer Activity and Mechanisms of Action
Protein & Peptide Letters Conformation as the Therapeutic Target for Neurodegenerative Diseases
Current Alzheimer Research Sphingosine Kinases Signalling in Carcinogenesis
Mini-Reviews in Medicinal Chemistry Pyrazolopyrimidine Derivatives as Antineoplastic Agents: with a Special Focus on Thyroid Cancer
Mini-Reviews in Medicinal Chemistry Oxidative stress and Parkinson’s disease: New hopes in treatment with herbal antioxidants
Current Pharmaceutical Design Functional Role of Glycosphingolipids in Cancer
Current Medicinal Chemistry Engagement of Renin-Angiotensin System in Prostate Cancer
Current Cancer Drug Targets Cell Cycle and Cancer: The G1 Restriction Point and the G1 / S Transition
Current Genomics Compartmentalized Platforms for Neuro-Pharmacological Research
Current Neuropharmacology Neurotoxic and Neuroactive Compounds from Cnidaria: Five Decades of Research….and More
Central Nervous System Agents in Medicinal Chemistry Silybin and Silymarin - New and Emerging Applications in Medicine
Current Medicinal Chemistry Genome-wide Analysis of Myelodysplastic Syndromes
Current Pharmaceutical Design Lysosomal Modulatory Drugs for a Broad Strategy Against Protein Accumulation Disorders
Current Alzheimer Research Amino Acid Degrading Enzymes and their Application in Cancer Therapy
Current Medicinal Chemistry Integrins in Bone Metastasis Formation and Potential Therapeutic Implications
Current Cancer Drug Targets Treatment of Insulin Resistance in the Neurodegeneration
Recent Patents on CNS Drug Discovery (Discontinued)