Abstract
Epinephrine and Norepinephrine, typically released during stress bind to nine different adrenoceptors (AR) which classically control the cardiovascular and respiratory systems. New targets were described for the many agonists and antagonists developed for these AR, as the central nervous system. During the last three decades, AR expression and action on the mammary gland/breast were extensively investigated. In the cow mammary gland, good milkability was associated with low density of β2-AR and high density of α2-AR. In the rat normal mammary gland, β-AR are expressed in the epithelial cells, alveoli, ducts, and adipocytes showing an exquisite regulation by steroid hormones and prolactin. In rat dimethylbenz(a)anthracene (DMBA) tumors, a close correlation was observed between tumor growth and β-AR concentration. β2-AR were described in numerous human cell lines and breast tumors. The action of β-adrenergic compounds on cell proliferation is contradictory. While some authors found that β-agonists significantly inhibit cancer cell proliferation and tumor growth in mice, others described a significant reduction in DNA synthesis by β-blockers. Also, positive effects of β-AR on human carcinoma cell migration have been described. α2-AR are expressed in human breast cancer and non-cancer cell lines, their stimulation being associated with increased cell proliferation. In vivo clonidine increased tumor growth and α2-adrenergic antagonists completely reversed this effect. When administered alone, rauwolscine inhibited tumor growth behaving as an inverse agonist. Therefore, the numerous adrenergic β- and α-AR agonists or antagonists could prove to be unexpected therapeutic options for mammary gland/ breast and mainly breast cancer.
Keywords: Beta-adrenoceptors, alpha-adrenoceptors, normal breast, breast cancer, mammary tumor
Current Medicinal Chemistry
Title: Adrenoceptors: Non Conventional Target for Breast Cancer?
Volume: 16 Issue: 15
Author(s): I A. Luthy, A. Bruzzone, C. Perez Pinero, L. F. Castillo, I. J. Chiesa, S. M. Vazquez and M. G. Sarappa
Affiliation:
Keywords: Beta-adrenoceptors, alpha-adrenoceptors, normal breast, breast cancer, mammary tumor
Abstract: Epinephrine and Norepinephrine, typically released during stress bind to nine different adrenoceptors (AR) which classically control the cardiovascular and respiratory systems. New targets were described for the many agonists and antagonists developed for these AR, as the central nervous system. During the last three decades, AR expression and action on the mammary gland/breast were extensively investigated. In the cow mammary gland, good milkability was associated with low density of β2-AR and high density of α2-AR. In the rat normal mammary gland, β-AR are expressed in the epithelial cells, alveoli, ducts, and adipocytes showing an exquisite regulation by steroid hormones and prolactin. In rat dimethylbenz(a)anthracene (DMBA) tumors, a close correlation was observed between tumor growth and β-AR concentration. β2-AR were described in numerous human cell lines and breast tumors. The action of β-adrenergic compounds on cell proliferation is contradictory. While some authors found that β-agonists significantly inhibit cancer cell proliferation and tumor growth in mice, others described a significant reduction in DNA synthesis by β-blockers. Also, positive effects of β-AR on human carcinoma cell migration have been described. α2-AR are expressed in human breast cancer and non-cancer cell lines, their stimulation being associated with increased cell proliferation. In vivo clonidine increased tumor growth and α2-adrenergic antagonists completely reversed this effect. When administered alone, rauwolscine inhibited tumor growth behaving as an inverse agonist. Therefore, the numerous adrenergic β- and α-AR agonists or antagonists could prove to be unexpected therapeutic options for mammary gland/ breast and mainly breast cancer.
Export Options
About this article
Cite this article as:
Luthy A. I, Bruzzone A., Pinero Perez C., Castillo F. L., Chiesa J. I., Vazquez M. S. and Sarappa G. M., Adrenoceptors: Non Conventional Target for Breast Cancer?, Current Medicinal Chemistry 2009; 16 (15) . https://dx.doi.org/10.2174/092986709788186048
DOI https://dx.doi.org/10.2174/092986709788186048 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
-
Pyrano[3,2-c]quinoline Derivatives as New Class of α-glucosidase Inhibitors to Treat Type 2 Diabetes: Synthesis, in vitro Biological Evaluation and Kinetic Study
Medicinal Chemistry A New Method to Measure P-gp (ABCB1) Activity
Drug Metabolism Letters Anti-Interleukin-6 Therapy for Crohns Disease
Current Pharmaceutical Design Procarbazine – A Traditional Drug in the Treatment of Malignant Gliomas
Current Medicinal Chemistry The Many Faces of MTA3 Protein in Normal Development and Cancers
Current Protein & Peptide Science Evaluating Potential P-gp Substrates: Main Aspects to Choose the Adequate Permeability Model for Assessing Gastrointestinal Drug Absorption
Mini-Reviews in Medicinal Chemistry Anticancer Agent Ukrain and Bortezomib Combination is Synergistic in 4T1 Breast Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry Molecular Biotheranostic Approaches of Cancers Using LAT Kit Probes
Current Medical Imaging Discovery of Hybrid Purine-quinoline Molecules and Their Cytotoxic Evaluation
Letters in Drug Design & Discovery The Role of P-Glycoprotein in Psychiatric Disorders: A Reliable Guard of the Brain?
Central Nervous System Agents in Medicinal Chemistry IgG4 Related Syndrome: Another Multiorgan Disease in the Interest Field of Internal Medicine
Current Pharmaceutical Design Intestinal Fibrosis in Crohns Disease: Medical Treatment or Surgery?
Current Drug Targets The Emerging Role of Vascular Endothelial Growth Factor (VEGF) in Vascular Homeostasis: Lessons from Recent Trials with Anti-VEGF Drugs
Current Vascular Pharmacology Recent Developments in Breast Tomosynthesis Imaging
Recent Patents on Medical Imaging Rational Design and Development of RDP58
Current Pharmaceutical Design Melatonin, a Potential Therapeutic Agent for Smooth Muscle-Related Pathological Conditions and Aging
Current Medicinal Chemistry Interrelated Roles for the Aryl Hydrocarbon Receptor and Hypoxia Inducible Factor-1α in the Immune Response to Infection
Current Immunology Reviews (Discontinued) Modulation of Hepatic MRP3/ABCC3 by Xenobiotics and Pathophysiological Conditions: Role in Drug Pharmacokinetics
Current Medicinal Chemistry In vivo Evaluation and Alzheimer’s Disease Treatment Outcome of siRNA Loaded Dual Targeting Drug Delivery System
Current Pharmaceutical Biotechnology Natural Compounds and Drug Discovery: Can Cnidarian Venom Play a Role?
Central Nervous System Agents in Medicinal Chemistry