Abstract
Muscarinic acetylcholine receptors (mAChR) are expressed in cells without nervous origin. mAChR are up-regulated in tumor cells and their stimulation can modulate tumor growth. In this work we investigated the ability of mAChR activation to induce tumor cell death. We studied the action of a combination of low doses of the muscarinic agonist carbachol plus paclitaxel, a chemotherapeutic agent frequently used in breast cancer treatment, in terms of effectiveness. Long term treatment with carbachol exerted anti-proliferative actions on LM2 and LM3 murine mammary adenocarcinoma cells, similarly to paclitaxel. The combination of carbachol with paclitaxel at submaximal concentrations, added during 20 h decreased tumor cell proliferation in a more potent manner than each drug added separately. This effect was reverted by the muscarinic antagonist atropine, and was due to a potentiation of tumor cell apoptosis tested by TUNEL assay. This treatment did not affect the proliferation of the non tumorigenic mammary cell line NMuMG. In conclusion, the combination of a muscarinic agonist plus paclitaxel should be tested as a useful therapeutic tool in breast cancer treatment.
Keywords: Apoptosis - breast cancer cells - muscarinic receptors - paclitaxel.
Anti-Cancer Agents in Medicinal Chemistry
Title:Muscarinic Activation Enhances the Anti-proliferative Effect of Paclitaxel in Murine Breast Tumor Cells
Volume: 13 Issue: 8
Author(s): Alejandro Javier Español, Guillermina Jacob, Ganna Dmytrenko and María Elena Sales
Affiliation:
Keywords: Apoptosis - breast cancer cells - muscarinic receptors - paclitaxel.
Abstract: Muscarinic acetylcholine receptors (mAChR) are expressed in cells without nervous origin. mAChR are up-regulated in tumor cells and their stimulation can modulate tumor growth. In this work we investigated the ability of mAChR activation to induce tumor cell death. We studied the action of a combination of low doses of the muscarinic agonist carbachol plus paclitaxel, a chemotherapeutic agent frequently used in breast cancer treatment, in terms of effectiveness. Long term treatment with carbachol exerted anti-proliferative actions on LM2 and LM3 murine mammary adenocarcinoma cells, similarly to paclitaxel. The combination of carbachol with paclitaxel at submaximal concentrations, added during 20 h decreased tumor cell proliferation in a more potent manner than each drug added separately. This effect was reverted by the muscarinic antagonist atropine, and was due to a potentiation of tumor cell apoptosis tested by TUNEL assay. This treatment did not affect the proliferation of the non tumorigenic mammary cell line NMuMG. In conclusion, the combination of a muscarinic agonist plus paclitaxel should be tested as a useful therapeutic tool in breast cancer treatment.
Export Options
About this article
Cite this article as:
Español Javier Alejandro, Jacob Guillermina, Dmytrenko Ganna and Sales Elena María, Muscarinic Activation Enhances the Anti-proliferative Effect of Paclitaxel in Murine Breast Tumor Cells, Anti-Cancer Agents in Medicinal Chemistry 2013; 13 (8) . https://dx.doi.org/10.2174/18715206113139990136
DOI https://dx.doi.org/10.2174/18715206113139990136 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...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
-
PI3K/Akt Signalling Pathway Specific Inhibitors: A Novel Strategy to Sensitize Cancer Cells to Anti-Cancer Drugs
Current Pharmaceutical Design Phosphorylation-Specific Prolyl Isomerase Pin1 as a new Diagnostic and Therapeutic Target for Cancer
Current Cancer Drug Targets Neurokinin Receptors and Subtypes as Potential Targets in Breast Cancer: Relevance to Bone Marrow Metastasis
Drug Design Reviews - Online (Discontinued) Heparanase as a Target in Cancer Therapy
Current Cancer Drug Targets Recent Advances in Transcranial Focused Ultrasound (FUS) Triggered Brain Delivery
Current Drug Targets The Design and Synthesis of Novel Phenothiazine Derivatives as Potential Cytotoxic Agents
Letters in Drug Design & Discovery Two Panels of Steroid Receptor Luciferase Reporter Cell Lines for Compound Profiling
Combinatorial Chemistry & High Throughput Screening Editorial (Thematic Issue: Endocrine Related Cancer: From Stem Cells to New Drug Targets)
Current Medicinal Chemistry 3-Substituted-3-hydroxy-2-oxindole, an Emerging New Scaffold for Drug Discovery with Potential Anti-Cancer and other Biological Activities
Current Bioactive Compounds Flavonoids as Anticancer Agents: Structure-Activity Relationship Study
Current Medicinal Chemistry - Anti-Cancer Agents Role of Colloidal Drug Delivery Carriers in Taxane-mediated Chemotherapy: A Review
Current Pharmaceutical Design Pharmacogenetics in Treatment of Rheumatoid Arthritis
Current Pharmaceutical Design Gene Therapy Using IL-12 Family Members in Infection, Auto-Immunity, and Cancer
Current Gene Therapy Menopausal Transition and Chronic Diseases
Current Women`s Health Reviews The 21st Century Form of Vitamin E - Tocotrienol
Current Pharmaceutical Design Dietary Supplement Therapies for Inflammatory Bowel Disease: Crohn’s Disease and Ulcerative Colitis
Current Pharmaceutical Design Cartilage Oligomeric Matrix Protein: Matricellular and Matricrine Signaling in Cardiovascular Homeostasis and Disease
Current Vascular Pharmacology Equol is Neuroprotective During Focal Cerebral Ischemia and Reperfusion that Involves p-Src and gp91<sup>phox</sup>
Current Neurovascular Research Phytochemicals in Anticancer Drug Development
Anti-Cancer Agents in Medicinal Chemistry Novel Strategies in Cancer Therapeutics: Targeting Enzymes Involved in Cell Cycle Regulation and Cellular Proliferation
Current Cancer Drug Targets