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
-
New Use for Old Drugs? Prospective Targets of Chloroquines in Cancer Therapy
Current Drug Targets Recent Advances of Fluorescent Technologies for Drug Discovery and Development
Current Pharmaceutical Design DNA Methylation and Breast Cancer
Current Genomics MicroRNAs in Renal Cell Carcinoma
MicroRNA The Link Between CD6 and Autoimmunity: Genetic and Cellular Associations
Current Drug Targets Spirulina paltensis: Food and Function
Current Nutrition & Food Science Drug Repurposing: An Emerging Tool for Drug Reuse, Recycling and Discovery
Current Drug Research Reviews Improved Candidate Biomarker Detection Based on Mass Spectrometry Data Using the Hilbert-Huang Transform
Protein & Peptide Letters Hydrogen Sulphide: Biopharmacological Roles in the Cardiovascular System and Pharmaceutical Perspectives
Current Medicinal Chemistry MicroRNA Gene Networks in Oncogenesis
Current Genomics Antitumor and Antiviral Activity of Pentacyclic Triterpenes
Mini-Reviews in Organic Chemistry Improved Drug Delivery System for Cancer Treatment by D-Glucose Conjugation with Eugenol From Natural Product
Current Drug Delivery Discovery of Anticancer Agents from 2-Pyrazoline-Based Compounds
Current Medicinal Chemistry Advances in Methods for Therapeutic Peptide Discovery, Design and Development
Current Pharmaceutical Biotechnology Drug Targeting Strategies in Cancer Treatment: An Overview
Mini-Reviews in Medicinal Chemistry Supramolecular Chiro-Biomedical Assays and Enantioselective HPLC Analyses for Evaluation of Profens as Non-Steroidal Anti-Inflammatory Drugs, Potential Anticancer Agents and Common Xenobiotics
Current Drug Discovery Technologies PPAR-Gamma in Ulcerative Colitis: A Novel Target for Intervention
Current Drug Targets Genetic Mapping of Pharmacogenetic Regulatory Variation
Current Pharmaceutical Design In Vivo Inhibition of Proteasome Activity and Tumour Growth by Murraya koenigii Leaf Extract in Breast Cancer Xenografts and by Its Active Flavonoids in Breast Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry Meet Our Editorial Board Member:
The Natural Products Journal