Abstract
Clinical treatment response achievable with conventional chemotherapy in high-grade osteosarcoma (OS) is severely limited by the presence of intrinsic or acquired drug resistance, which in previous studies has been mainly addressed for overexpression of ABCB1 (MDR1/P-glycoprotein). This study was aimed to estimate the impact on OS drug resistance of a group of ATP binding cassette (ABC) transporters, which in other human tumors have been associated with unresponsiveness to the drugs that represent the backbone of multidrug treatment regimens for OS (doxorubicin, methotrexate, cisplatin).
By using a group of 6 drug-sensitive and 20 drug-resistant human OS cell lines, the most relevant transporter which proved to be associated with the degree of drug resistance in OS cells, in addition to ABCB1, was ABCC1. We therefore evaluated the in vitro activity of the orally administrable ABCB1/ABCC1 inhibitor CBT-1® (Tetrandrine, NSC-77037). We found that in our OS cell lines this agent was able to revert the ABCB1/ABCC1-mediated resistance against doxorubicin, as well as against the drugs used in second-line OS treatments that are substrates of these transporters (taxotere, etoposide, vinorelbine). Our findings indicated that inhibiting ABCB1 and ABCC1 with CBT-1®, used in association with conventional chemotherapeutic drugs, may become an interesting new therapeutic option for unresponsive or relapsed OS patients.
Keywords: ABC transporters, chemosensitization, chemotherapy, drug resistance, osteosarcoma, tailored treatments.
Current Cancer Drug Targets
Title:Targeting ABCB1 and ABCC1 with their Specific Inhibitor CBT-1® can Overcome Drug Resistance in Osteosarcoma
Volume: 16 Issue: 3
Author(s): Marilù Fanelli, Claudia Maria Hattinger, Serena Vella, Elisa Tavanti, Francesca Michelacci, Beth Gudeman, Daryl Barnett, Piero Picci and Massimo Serra
Affiliation:
Keywords: ABC transporters, chemosensitization, chemotherapy, drug resistance, osteosarcoma, tailored treatments.
Abstract: Clinical treatment response achievable with conventional chemotherapy in high-grade osteosarcoma (OS) is severely limited by the presence of intrinsic or acquired drug resistance, which in previous studies has been mainly addressed for overexpression of ABCB1 (MDR1/P-glycoprotein). This study was aimed to estimate the impact on OS drug resistance of a group of ATP binding cassette (ABC) transporters, which in other human tumors have been associated with unresponsiveness to the drugs that represent the backbone of multidrug treatment regimens for OS (doxorubicin, methotrexate, cisplatin).
By using a group of 6 drug-sensitive and 20 drug-resistant human OS cell lines, the most relevant transporter which proved to be associated with the degree of drug resistance in OS cells, in addition to ABCB1, was ABCC1. We therefore evaluated the in vitro activity of the orally administrable ABCB1/ABCC1 inhibitor CBT-1® (Tetrandrine, NSC-77037). We found that in our OS cell lines this agent was able to revert the ABCB1/ABCC1-mediated resistance against doxorubicin, as well as against the drugs used in second-line OS treatments that are substrates of these transporters (taxotere, etoposide, vinorelbine). Our findings indicated that inhibiting ABCB1 and ABCC1 with CBT-1®, used in association with conventional chemotherapeutic drugs, may become an interesting new therapeutic option for unresponsive or relapsed OS patients.
Export Options
About this article
Cite this article as:
Fanelli Marilù, Hattinger Maria Claudia, Vella Serena, Tavanti Elisa, Michelacci Francesca, Gudeman Beth, Barnett Daryl, Picci Piero and Serra Massimo, Targeting ABCB1 and ABCC1 with their Specific Inhibitor CBT-1® can Overcome Drug Resistance in Osteosarcoma, Current Cancer Drug Targets 2016; 16 (3) . https://dx.doi.org/10.2174/1568009616666151106120434
DOI https://dx.doi.org/10.2174/1568009616666151106120434 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...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
Related Articles
-
Facile Synthesis of Stereoisomers of the Non-Secosteroidal Ligand LG190178 and their Evaluation Using the Mutant Vitamin D Receptor
Letters in Organic Chemistry Apoptotic Potency of Angiostatic Compounds in the Treatment of Cancer
Current Pharmaceutical Biotechnology Cancer T Cell Immunotherapy with Bispecific Antibodies and Chimeric Antigen Receptors
Recent Patents on Anti-Cancer Drug Discovery Role of Wnt/β-catenin Signaling in Drug Resistance of Pancreatic Cancer
Current Pharmaceutical Design Targeting the Wingless Signaling Pathway with Natural Compounds as Chemopreventive or Chemotherapeutic Agents
Current Pharmaceutical Biotechnology Bleomycin Induced Sensitivity to TRAIL/Apo-2L-Mediated Apoptosis in Human Seminomatous Testicular Cancer Cells is Correlated with Upregulation of Death Receptors
Anti-Cancer Agents in Medicinal Chemistry RAN GTPase as a Target for Cancer Therapy: Ran Binding Proteins
Current Molecular Medicine Kinase Phosphorylation-based Mechanisms of PARP Inhibitor Resistance During Synthetic Lethal Oncotherapy
Current Signal Transduction Therapy MiR-22-3p Regulates Amyloid β Deposit in Mice Model of Alzheimer's Disease by Targeting Mitogen-activated Protein Kinase 14
Current Neurovascular Research Quantitative Analysis of Acidic Polysaccharides Using Hydrophilic Interaction Chromatography and Mass Spectrometry after Acid Hydrolysis
Current Pharmaceutical Analysis Patents in Cancer Stem Cells
Recent Patents on Biomarkers Enhanced Pro-Apoptotic Effect of Tetrandrine Loaded Nanoparticles Against Osteosarcoma Cells
Current Drug Delivery Curcumin: Not So Spicy After All
Mini-Reviews in Medicinal Chemistry microRNAs in Cancer: Lessons from Melanoma
Current Pharmaceutical Design Autophagy Regulators as Potential Cancer Therapeutic agents: A Review
Current Topics in Medicinal Chemistry CypA: A Potential Target of Tumor Radiotherapy and/or Chemotherapy
Current Medicinal Chemistry The Application of Natural Products in Cancer Therapy by Targeting Apoptosis Pathways
Current Drug Metabolism Targeting Interleukin-1β for Pain
CNS & Neurological Disorders - Drug Targets Thymoquinone Inhibits Proliferation and Migration of MDA-MB-231 Triple Negative Breast Cancer Cells by Suppressing Autophagy, Beclin-1 and LC3
Anti-Cancer Agents in Medicinal Chemistry Genome and Transcriptome Analysis of Neuroblastoma Advanced Diagnosis from Innovative Therapies
Current Pharmaceutical Design