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
-
Vertebrate Protein CTCF and its Multiple Roles in a Large-Scale Regulation of Genome Activity
Current Genomics Nitrogen Mustards as Anticancer Chemotherapies: Historic Perspective, Current Developments and Future Trends
Current Topics in Medicinal Chemistry Pharmacogenomics in Drug Induced Liver Injury
Current Drug Metabolism Effective Inhibition of Mitochondrial Metabolism by Cryptotanshinone in MDA-MB231 cells: A Proteomic Analysis
Current Proteomics The Akt/PKB Family of Protein Kinases: A Review of Small Molecule Inhibitors and Progress Towards Target Validation
Current Topics in Medicinal Chemistry Wnt / β-Catenin Signaling Pathway as Novel Cancer Drug Targets
Current Cancer Drug Targets Radiolabeled Compounds in Diagnosis of Infectious and Inflammatory Disease
Current Pharmaceutical Design Network Effect of Wt-mutant p53 Interactions and Implications on p53 Gene Therapy
Current Pharmaceutical Design Circulating Tumor Stem Cells as Biomarkers for Cancer Progression
Recent Patents on Biomarkers Personalized Diabetes and Cancer Medicine: A Rationale for Anti-Diabetic Nutrition (Bitter Melon) in a Supportive Setting
Current Cancer Therapy Reviews Targeted Enzyme Prodrug Therapies
Mini-Reviews in Medicinal Chemistry The Pathogenic Role of Intestinal Flora in IBD and Colon Cancer
Current Drug Targets Preparation and Characterization of Amine- and Carboxylic Acid-functionalized Superparamagnetic Iron Oxide Nanoparticles Through a One-step Facile Electrosynthesis Method
Current Nanoscience Editorial (Thematic Issue: Signal Transduction, Targeted Therapy and Cancer: From Bench to Clinics)
Current Pharmaceutical Design Radionuclide Therapy of Cancer with Radiolabeled Antibodies
Anti-Cancer Agents in Medicinal Chemistry Role of Netrin-1 Beyond the Brain: From Biomarker of Tissue Injury to Therapy for Inflammatory Diseases
Recent Patents on Biomarkers Quantitative Analysis of UGT2B28 mRNA Expression by Real-Time RT-PCR and Application to Human Tissue Distribution Study
Drug Metabolism Letters MicroRNA-dependent Regulation of Telomere Maintenance Mechanisms: A Field as Much Unexplored as Potentially Promising
Current Pharmaceutical Design The Traces of Sound: Taking the Road to Skin
Current Rheumatology Reviews The Hydrocarbon Staple & Beyond: Recent Advances Towards Stapled Peptide Therapeutics that Target Protein-Protein Interactions
Current Topics in Medicinal Chemistry