Abstract
Breast cancer resistant protein (BCRP, ABCG2) is an ATP-binding cassette (ABC) transporter, which together with two other ABC efflux drug pumps, namely P-glycoprotein (P-gp, ABCB1) and multidrug resistance-related protein 1 (MRP1, ABCC1) is the most important multidrug resistance protein foun d in eukaryotic cells including cells in the testis. However, unlike P-gp and MRP1, which are components of the Sertoli cell blood-testis barrier (BTB), BCRP is not expressed at the BTB in rodents and human testes. Instead, BCRP is expressed by peritubular myoid cells and endothelial cells of the lymphatic vessel in the tunica propria, residing outside the BTB. As such, the testis is equipped with two levels of defense against xenobiotics or drugs, preventing these harmful substances from entering the adluminal compartment to perturb meiosis and post-meiotic spermatid development: one at the level of the BTB conferred by P-gp and MRP1 and one at the tunica propria conferred by BCRP. The presence of drug transporters at the tunica propria as well as at the Sertoli cell BTB thus poses significant obstacles in developing non-hormonal contraceptives if these drugs (e.g., adjudin) exert their effects in germ cells behind the BTB, such as in the adluminal (apical) compartment of the seminiferous epithelium. Herein, we summarize recent findings pertinent to adjudin, a non-hormonal male contraceptive, and molecular interactions of adjudin with BCRP so that this information can be helpful to devise delivery strategies to evade BCRP in the tunica propria to improve its bioavailability in the testis.
Keywords: Adjudin, male contraceptive, anti-cancer drug, breast cancer resistance protein, ectoplasmic specialization, spermatogenesis, testis.
Current Molecular Pharmacology
Title:Interaction of Oligomeric Breast Cancer Resistant Protein (BCRP) with Adjudin: A Male Contraceptive with Anti-Cancer Activity
Volume: 7
Author(s): Yan H. Cheng, Pranitha Jenardhanan, Premendu P. Mathur, Xiaojing Qian, Weiliang Xia, Bruno Silvestrini and Chuen Y. Cheng
Affiliation:
Keywords: Adjudin, male contraceptive, anti-cancer drug, breast cancer resistance protein, ectoplasmic specialization, spermatogenesis, testis.
Abstract: Breast cancer resistant protein (BCRP, ABCG2) is an ATP-binding cassette (ABC) transporter, which together with two other ABC efflux drug pumps, namely P-glycoprotein (P-gp, ABCB1) and multidrug resistance-related protein 1 (MRP1, ABCC1) is the most important multidrug resistance protein foun d in eukaryotic cells including cells in the testis. However, unlike P-gp and MRP1, which are components of the Sertoli cell blood-testis barrier (BTB), BCRP is not expressed at the BTB in rodents and human testes. Instead, BCRP is expressed by peritubular myoid cells and endothelial cells of the lymphatic vessel in the tunica propria, residing outside the BTB. As such, the testis is equipped with two levels of defense against xenobiotics or drugs, preventing these harmful substances from entering the adluminal compartment to perturb meiosis and post-meiotic spermatid development: one at the level of the BTB conferred by P-gp and MRP1 and one at the tunica propria conferred by BCRP. The presence of drug transporters at the tunica propria as well as at the Sertoli cell BTB thus poses significant obstacles in developing non-hormonal contraceptives if these drugs (e.g., adjudin) exert their effects in germ cells behind the BTB, such as in the adluminal (apical) compartment of the seminiferous epithelium. Herein, we summarize recent findings pertinent to adjudin, a non-hormonal male contraceptive, and molecular interactions of adjudin with BCRP so that this information can be helpful to devise delivery strategies to evade BCRP in the tunica propria to improve its bioavailability in the testis.
Export Options
About this article
Cite this article as:
H. Cheng Yan, Jenardhanan Pranitha, P. Mathur Premendu, Qian Xiaojing, Xia Weiliang, Silvestrini Bruno and Y. Cheng Chuen, Interaction of Oligomeric Breast Cancer Resistant Protein (BCRP) with Adjudin: A Male Contraceptive with Anti-Cancer Activity, Current Molecular Pharmacology 2014; 7 (2) . https://dx.doi.org/10.2174/1874467208666150126154049
DOI https://dx.doi.org/10.2174/1874467208666150126154049 |
Print ISSN 1874-4672 |
Publisher Name Bentham Science Publisher |
Online ISSN 1874-4702 |

- Author Guidelines
- Bentham Author Support Services (BASS)
- 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
-
Omega-3 Polyunsaturated Fatty Acid Derived Lipid Mediators and their Application in Drug Discovery
Current Medicinal Chemistry Nitric Oxide, Peroxynitrite, Peroxynitrous Acid, Nitroxyl, Nitrogen Dioxide, Nitrous Oxide: Biochemical Mechanisms and Bioaction
Current Bioactive Compounds The Exploitation of Toll-like Receptor 3 Signaling in Cancer Therapy
Current Pharmaceutical Design FDG-PET Imaging in Large Vessel Vasculitis and Polymyalgia Rheumatica: A Personal View
Current Immunology Reviews (Discontinued) Biological Responses to Hydrogen Molecule and its Preventive Effects on Inflammatory Diseases
Current Pharmaceutical Design Computer Aided Drug Design Approaches for Identification of Novel Autotaxin (ATX) Inhibitors
Current Medicinal Chemistry PI3K/Akt Signalling Pathway Specific Inhibitors: A Novel Strategy to Sensitize Cancer Cells to Anti-Cancer Drugs
Current Pharmaceutical Design Voltage-Gated Sodium Channel Blockers as Immunomodulators
Recent Patents on CNS Drug Discovery (Discontinued) Development of Molecular Targeted Anticancer Agents: Successes, Failures and Future Directions
Current Pharmaceutical Design Importance of Kier-Hall Topological Indices in the QSAR of Anticancer Drug Design
Current Computer-Aided Drug Design The Biphasic Expression Pattern of miR-200a and E-cadherin in Epithelial Ovarian Cancer and its Correlation with Clinicopathological Features
Current Pharmaceutical Design The Medical and Medico-legal Complications of Bulimia Nervosa : Treatments and Complications
Current Women`s Health Reviews Nanoparticle-Based Combination Therapy for Cancer Treatment
Current Pharmaceutical Design Targeting CNS Transporters for Treatment of Neurodegenerative Diseases
Current Pharmaceutical Design Emerging Therapies in the Treatment of Locally Advanced Squamous Cell Cancers of Head and Neck
Recent Patents on Anti-Cancer Drug Discovery Bacteria and Bacterial Toxins as Therapeutic Agents for Solid Tumors
Current Cancer Drug Targets Novel Indole-Isoxazole Hybrids: Synthesis and In Vitro Anti-Cholinesterase Activity
Letters in Drug Design & Discovery Moving Beyond VEGF for Anti-angiogenesis Strategies in Gynecologic Cancer
Current Pharmaceutical Design Immunogenicity and Immunomodulatory Properties of Hepatocyte-like Cells Derived from Human Amniotic Epithelial Cells
Current Stem Cell Research & Therapy The Beneficial Role of Vitamin D in Human Immunodeficiency Virus Infection
Current HIV Research