Abstract
Aims: The mechanisms behind cellular anthracycline uptake are not completely understood. Knowledge about uptake mechanisms could be used to increase the selectivity of the drugs. We compared the uptake patterns of, daunorubicin (DNR), doxorubicin (DOX), epirubicin (EPI), idarubicin (IDA), and pirarubicin (PIRA) by cultured leukemic cells and investigated possible involvement of specific carriers. Methods: HL-60 cells were incubated with anthracyclines for 1 hour in the absence or presence of transport inhibitors, suramin, or nucleosides and cellular drug uptake was determined. Cell survival was also determined. MCF-7 breast cancer cells were used as a negative control for concentrative nucleoside transporters (CNTs). Anthracycline concentration was determined with HPLC and fluorometric detection and apoptosis was determined with propidium iodide and flow cytometry. Results: DNR, IDA, and PIRA had higher uptake than DOX and EPI with a prominent increase in uptake at concentrations > 1 µM. Uptake of all anthracyclines was greatly reduced at 0°C. Suramin, a purinergic-2-receptor inhibitor, strongly inhibited the uptake of all anthracyclines except PIRA and increased cell survival. Dipyridamole, an equilibrative NT (ENT) inhibitor, significantly inhibited the uptake of DNR only. The addition of nucleosides significantly inhibited the uptake of DNR, IDA, and PIRA but not in MCF-7 cells lacking functional CNTs. Conclusion: Our results suggest different uptake mechanisms for the anthracyclines studied. We found evidence for carrier mediated uptake mechanisms, supporting involvement of NTs in transmembrane transport of DNR, IDA, and PIRA. The results also showed a strong inhibition of suramin on anthracycline uptake by so far unknown mechanisms.
Keywords: Anthracyclines, leukemic cells, nucleoside transporters, suramin, uptake.
Current Drug Delivery
Title:Comparison of Uptake Mechanisms for Anthracyclines in Human Leukemic Cells
Volume: 10 Issue: 4
Author(s): Hazhar Karim, Alex Bogason, Hasanuzzaman Bhuiyan, Alan K. Fotoohi, Pierre Lafolie and Sigurd Vitols
Affiliation:
Keywords: Anthracyclines, leukemic cells, nucleoside transporters, suramin, uptake.
Abstract: Aims: The mechanisms behind cellular anthracycline uptake are not completely understood. Knowledge about uptake mechanisms could be used to increase the selectivity of the drugs. We compared the uptake patterns of, daunorubicin (DNR), doxorubicin (DOX), epirubicin (EPI), idarubicin (IDA), and pirarubicin (PIRA) by cultured leukemic cells and investigated possible involvement of specific carriers. Methods: HL-60 cells were incubated with anthracyclines for 1 hour in the absence or presence of transport inhibitors, suramin, or nucleosides and cellular drug uptake was determined. Cell survival was also determined. MCF-7 breast cancer cells were used as a negative control for concentrative nucleoside transporters (CNTs). Anthracycline concentration was determined with HPLC and fluorometric detection and apoptosis was determined with propidium iodide and flow cytometry. Results: DNR, IDA, and PIRA had higher uptake than DOX and EPI with a prominent increase in uptake at concentrations > 1 µM. Uptake of all anthracyclines was greatly reduced at 0°C. Suramin, a purinergic-2-receptor inhibitor, strongly inhibited the uptake of all anthracyclines except PIRA and increased cell survival. Dipyridamole, an equilibrative NT (ENT) inhibitor, significantly inhibited the uptake of DNR only. The addition of nucleosides significantly inhibited the uptake of DNR, IDA, and PIRA but not in MCF-7 cells lacking functional CNTs. Conclusion: Our results suggest different uptake mechanisms for the anthracyclines studied. We found evidence for carrier mediated uptake mechanisms, supporting involvement of NTs in transmembrane transport of DNR, IDA, and PIRA. The results also showed a strong inhibition of suramin on anthracycline uptake by so far unknown mechanisms.
Export Options
About this article
Cite this article as:
Karim Hazhar, Bogason Alex, Bhuiyan Hasanuzzaman, Fotoohi K. Alan, Lafolie Pierre and Vitols Sigurd, Comparison of Uptake Mechanisms for Anthracyclines in Human Leukemic Cells, Current Drug Delivery 2013; 10 (4) . https://dx.doi.org/10.2174/1567201811310040005
DOI https://dx.doi.org/10.2174/1567201811310040005 |
Print ISSN 1567-2018 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5704 |
Call for Papers in Thematic Issues
Advances of natural products, bio-actives and novel drug delivery system against emerging viral infections
Due to the increasing prevalence of viral infections and the ability of these human pathogens to develop resistance to current treatment strategies, there is a great need to find and develop new compounds to combat them. These molecules must have low toxicity, specific activity and high bioavailability. The most suitable ...read more
Electrospun Fibers as Drug Delivery Systems
In recent years, electrospun fibers have attracted considerable attention as potential platforms for drug delivery due to their distinctive properties and adaptability. These fibers feature a notable surface area-to-volume ratio and can be intentionally designed with high porosity, facilitating an increased capacity for drug loading and rendering them suitable for ...read more
Emerging Nanotherapeutics for Mitigation of Neurodegenerative Disorders
Conditions affecting the central nervous system (CNS) present a significant hurdle due to limited access of both treatments and diagnostic tools for the brain. The blood-brain barrier (BBB) acts as a barrier, restricting the passage of molecules from the bloodstream into the brain. The most formidable challenge facing scientists is ...read more
Nanotechnology Based Chemotherapy for the treatment of Head & Neck Cancer
The escalating recurrence rates observed in Head and Neck cancer, particularly within the chemo-therapeutically treated cohort (50-60%), can be attributed to the non-selective nature of current anticancer drug delivery modalities. In this context, nanotechnology-based drug delivery systems emerge as a promising avenue for achieving precise localization of therapeutic agents to ...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
-
Preclinical Toxicity of Paclitaxel Biopolymer Formulation
Anti-Cancer Agents in Medicinal Chemistry LncRNA as a Therapeutic Target for Angiogenesis
Current Topics in Medicinal Chemistry Regulatory Roles of Amino Acids in Immune Response
Current Rheumatology Reviews Potential Application of Biliverdin Reductase and its Fragments to Modulate insulin/IGF-1/MAPK/PI3-K Signaling Pathways in Therapeutic Settings
Current Drug Targets Long Non-Coding RNA: An Emerging Paradigm of Pancreatic Cancer
Current Molecular Medicine Antineoplastic Chemotherapy Induced QTc Prolongation
Current Drug Safety Cerenkov Luminescence Imaging at a Glance
Current Molecular Imaging (Discontinued) Recent Developments in Targeted Therapies of the RAF-MEK and PI3KAKT Pathways in Cancer Treatment
Current Cancer Therapy Reviews Ceramide and Apoptosis: Exploring the Enigmatic Connections between Sphingolipid Metabolism and Programmed Cell Death
Anti-Cancer Agents in Medicinal Chemistry Castration Resistant Prostate Cancer: From Emerging Molecular Pathways to Targeted Therapeutic Approaches
Clinical Cancer Drugs Herbal Medicines for Diabetes Management and its Secondary Complications
Current Diabetes Reviews Feasibility of Assam Bora Rice Starch as a Compression Coat of 5-Fluorouracil Core Tablet for Colorectal Cancer
Current Drug Delivery Dual Inhibitors of PI3K/mTOR or mTOR-Selective Inhibitors: Which Way Shall We Go?
Current Medicinal Chemistry Curcumin: Powerful Immunomodulator from Turmeric
Current Immunology Reviews (Discontinued) Vascular Endothelial Growth Factor and Its Receptor as Drug Targets in Hematological Malignancies
Current Drug Targets Based on Nucleotides Analysis of Tumor Cell Lines to Construct and Validate a Prediction Model of Mechanisms of Chemotherapeutics
Anti-Cancer Agents in Medicinal Chemistry Bioactivity of Hybrid Polymeric Magnetic Nanoparticles and Their Applications in Drug Delivery
Current Pharmaceutical Design Corticotropin Releasing Factor (CRF) Peptide Family and their Receptors: Divergent Actions Influencing Human Physiology
Current Genomics The Genomic Approaches to Major Depression
Current Pharmacogenomics Synthesis, Aromatase Inhibitory, Antiproliferative and Molecular Modeling Studies of Functionally Diverse D-Ring Pregnenolone Pyrazoles
Anti-Cancer Agents in Medicinal Chemistry