Abstract
The multidrug resistance (MDR) proteins are member of the ATP-binding cassette superfamily and are present in a majority of human tumors. Their activity is a crucial factor leading to therapeutic failure. It is likely that compounds which inhibit the function of the MDR-efflux proteins such as MDR1 will improve the cytotoxic action of anticancer chemotherapy. Therefore, a search for MDR reversing compounds was conducted among three classes of plant derived compounds such as diterpenes, triterpenes and carotenoids in a hope to find inhibitors without adverse effects in these natural compounds. The inhibition of efflux activity was determined by measuring the accumulation of substrate analogues such as rhodamine in tumor cells in the presence of potential inhibitors. Thus we determined the effect of structurally unrelated diterpenes, triterpenes and carotenoids on reversal of multidrug resistance in MDR-1 gene-transfected L1210 mouse lymphoma cells and MDR mediated multidrug resistance of human breast cancer cells MDA-MB-231 (HTB-26) and MCF-7. The majority of diterpenes, cycloartane triterpenes and carotenoids isolated from vegetables and medicinal plants were able to enhance rhodamine 123 accumulations of MDR-cells. Synergistic interaction was found between epirubicine and resistance modifier terpenoids in vitro. It is supposed that these MDR modulators bind into transmembrane domains and the action of ABC transporters is inhibited by induced conformational changes.
Keywords: Multidrug resistance, cancer cells, diterpenoids, triterpenoids, carotenoids
Current Pharmaceutical Design
Title: Inhibition of Multidrug Resistance of Cancer Cells by Natural Diterpenes, Triterpenes and Carotenoids
Volume: 12 Issue: 3
Author(s): Joseph Molnar, Nora Gyemant, Masaru Tanaka, Judith Hohmann, Elke Bergmann-Leitner, Peter Molnar, Joseph Deli, Remigijus Didiziapetris and Maria J. U. Ferreira
Affiliation:
Keywords: Multidrug resistance, cancer cells, diterpenoids, triterpenoids, carotenoids
Abstract: The multidrug resistance (MDR) proteins are member of the ATP-binding cassette superfamily and are present in a majority of human tumors. Their activity is a crucial factor leading to therapeutic failure. It is likely that compounds which inhibit the function of the MDR-efflux proteins such as MDR1 will improve the cytotoxic action of anticancer chemotherapy. Therefore, a search for MDR reversing compounds was conducted among three classes of plant derived compounds such as diterpenes, triterpenes and carotenoids in a hope to find inhibitors without adverse effects in these natural compounds. The inhibition of efflux activity was determined by measuring the accumulation of substrate analogues such as rhodamine in tumor cells in the presence of potential inhibitors. Thus we determined the effect of structurally unrelated diterpenes, triterpenes and carotenoids on reversal of multidrug resistance in MDR-1 gene-transfected L1210 mouse lymphoma cells and MDR mediated multidrug resistance of human breast cancer cells MDA-MB-231 (HTB-26) and MCF-7. The majority of diterpenes, cycloartane triterpenes and carotenoids isolated from vegetables and medicinal plants were able to enhance rhodamine 123 accumulations of MDR-cells. Synergistic interaction was found between epirubicine and resistance modifier terpenoids in vitro. It is supposed that these MDR modulators bind into transmembrane domains and the action of ABC transporters is inhibited by induced conformational changes.
Export Options
About this article
Cite this article as:
Molnar Joseph, Gyemant Nora, Tanaka Masaru, Hohmann Judith, Bergmann-Leitner Elke, Molnar Peter, Deli Joseph, Didiziapetris Remigijus and Ferreira J. U. Maria, Inhibition of Multidrug Resistance of Cancer Cells by Natural Diterpenes, Triterpenes and Carotenoids, Current Pharmaceutical Design 2006; 12 (3) . https://dx.doi.org/10.2174/138161206775201893
DOI https://dx.doi.org/10.2174/138161206775201893 |
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
-
Nanoparticles for Cancer Targeting: Current and Future Directions
Current Drug Delivery Estrogen Receptor-Positive and Estrogen Receptor-Negative Human Breast Cancer Cells: Regulation of Expression of Cancer-Related Genes by Estradiol and Tamoxifen
Current Signal Transduction Therapy Bothrops pauloensis Snake Venom Toxins: The Search for New Therapeutic Models
Current Topics in Medicinal Chemistry Human ABC Transporters at blood-CNS Interfaces as Determinants of CNS Drug Penetration
Current Pharmaceutical Design Outline of Proteins and Signaling Pathways Involved in Heart Failure
Current Protein & Peptide Science Tumor Systems Need to be Rendered Usable for a New Action-Theoretical Abstraction: The Starting Point for Novel Therapeutic Options
Current Cancer Therapy Reviews Context-dependent Action of Transforming Growth Factor β Family Members on Normal and Cancer Stem Cells
Current Pharmaceutical Design Technology Whitespaces India Should Focus: A Comparative Anti-Cancer Patent Rational Analysis of Indian and International Public Funded Universities
Recent Patents on Anti-Cancer Drug Discovery B Cell Modulation Strategies in Autoimmunity: The SLE Example
Current Pharmaceutical Design Patient-Tailored Treatments with Anti-EGFR Monoclonal Antibodies in Advanced Colorectal Cancer: KRAS and Beyond
Current Cancer Drug Targets ABC Transporters as Potential Targets for Modulation of Drug Resistance
Mini-Reviews in Medicinal Chemistry The Therapeutic Potential of Microencapsulate Implants: Patents and Clinical Trials
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Inhibitors of Nitrogen Oxide Species Production in Animal Models of Inflammation and Future Directions for Therapy in Inflammatory Disorders
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Effects of LPA and S1P on the Nervous System and Implications for Their Involvement in Disease
Current Drug Targets Novel Antibody Therapeutics Targeting Mesothelin In Solid Tumors
Clinical Cancer Drugs Chronic Inflammatory Diseases: Progress and Prospect with Herbal Medicine
Current Pharmaceutical Design Role of Graphene Nano-Composites in Cancer Therapy: Theranostic Applications, Metabolic Fate and Toxicity Issues
Current Drug Metabolism Roles of Natural Compounds from Medicinal Plants in Cancer Treatment: Structure and Mode of Action at Molecular Level
Medicinal Chemistry Nutrition in Adult Patients with Inflammatory Bowel Disease
Current Drug Targets Quinolones in the Search for New Anticancer Agents
Current Pharmaceutical Design