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
-
Cyclin-Dependent Kinase as a Novel Therapeutic Target: An Endless Story
Current Chemical Biology Management of Osteoporosis: Seeing the Future
Medicinal Chemistry Reviews - Online (Discontinued) Applications of Nanosystems to Anticancer Drug Therapy (Part II. Dendrimers, Micelles, Lipid-based Nanosystems)
Recent Patents on Anti-Cancer Drug Discovery LHON: Mitochondrial Mutations and More
Current Genomics Regulatory Roles of the Ubiquitin-Proteasome System in Cardiomyocyte Apoptosis
Current Molecular Medicine Tumoural Expression of Connective Tissue Growth Factor (CTGF) Impacts on Survival in Patients Diagnosed with Hepatocellular Carcinoma (HCC)
Current Cancer Drug Targets DLEU2: A Meaningful Long Noncoding RNA in Oncogenesis
Current Pharmaceutical Design Sida cordifolia, a Traditional Herb in Modern Perspective – A Review
Current Traditional Medicine Cucurbitacin IIb from Ibervillea sonorae Induces Apoptosis and Cell Cycle Arrest via STAT3 Inhibition
Anti-Cancer Agents in Medicinal Chemistry Beyond Thymidylate Synthase and Dihydrofolate Reductase: Impact of Non-coding microRNAs in Anticancer Chemoresistance
Current Enzyme Inhibition Potentials of Hydrogels in Cancer Therapy
Current Cancer Therapy Reviews Endothelial Lipase: A Key Player in HDL Metabolism Modulates Inflammation and Atherosclerotic Risk
Mini-Reviews in Medicinal Chemistry Exosome-like Nanoparticles: A New Type of Nanocarrier
Current Medicinal Chemistry An Investigative Approach to Treatment Modalities for Squamous Cell Carcinoma of Skin
Current Drug Delivery Mitocans: Mitochondrial Targeted Anti-Cancer Drugs as Improved Therapies and Related Patent Documents
Recent Patents on Anti-Cancer Drug Discovery A Comprehensive Review of the Genus Pyrola Herbs in Traditional Uses, Phytochemistry and Pharmacological Activities
Current Topics in Medicinal Chemistry From Multiple PAR1 Receptor/Protein Interactions to their Multiple Therapeutic Implications
Current Topics in Medicinal Chemistry Role of Microtubules Network in CYP Genes Expression
Current Drug Metabolism Meet Our Editorial Board Member
Anti-Cancer Agents in Medicinal Chemistry Chitosan Applications on Pharmaceutical Sciences: A Review
Drug Delivery Letters