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
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
-
Drug-Induced Thromboembolic Events in Patients with Malignancy
Cardiovascular & Hematological Disorders-Drug Targets Engineered Silver Nanoparticles, A New Nanoweapon Against Cancer
Anti-Cancer Agents in Medicinal Chemistry Pulmonary Neuroendocrine Cell System in Health and Disease
Current Respiratory Medicine Reviews Choice of Biologic Therapy for Patients with Rheumatoid Arthritis: The Infection Perspective
Current Rheumatology Reviews Review: The Role of Radiolabeled DOTA-Conjugated Peptides for Imaging and Treatment of Childhood Neuroblastoma
Current Radiopharmaceuticals Histamine H4 Receptor: A Novel Therapeutic Target for Immune and Allergic Responses
Mini-Reviews in Medicinal Chemistry Omega – 3 Fatty Acids as Pharmacotherapeutics in Psoriasis: Current Status and Scope of Nanomedicine in its Effective Delivery
Current Drug Targets Preparation and Primary Bioevaluation of 99mTc-labeled-1-thio-β-D-Glucose as Melanoma Targeting Agent
Current Radiopharmaceuticals Estrogen Receptor Alpha: Impact of Ligands on Intracellular Shuttling and Turnover Rate in Breast Cancer Cells
Current Cancer Drug Targets Tumor-Associated Macrophages as Potential Targets for Anti-Cancer Activity of Marine Invertebrate-Derived Compounds
Current Pharmaceutical Design Platelet Function in Inflammatory Diseases: Insights from Clinical Studies
Inflammation & Allergy - Drug Targets (Discontinued) Role of Translocator Protein in Renal Ischemia Reperfusion, Renal Preservation and Acute Kidney Injury
Current Molecular Medicine Role of Cervical Cancer Radiotherapy in the Expression of EGFR and p53 Gene
Current Proteomics Current Evaluation of the Millennium Phytomedicine- Ginseng (II): Collected Chemical Entities, Modern Pharmacology, and Clinical Applications Emanated from Traditional Chinese Medicine
Current Medicinal Chemistry Role of Genomic Alterations in HER2 Positive Breast Carcinoma: Focus on Susceptibility and Trastuzumab-therapy
Current Cancer Drug Targets Nutlins and Ionizing Radiation in Cancer Therapy
Current Pharmaceutical Design Concise Synthesis of 1,1-Diarylvinyl Sulfones and Investigations on their Antiproliferative Activity <i>via</i> Tubulin Inhibition
Anti-Cancer Agents in Medicinal Chemistry Aromatase Inhibitors and Inactivators for the Treatment of Postmenopausal Breast Cancer: A Review
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Mesenchymal Stromal Cells; Role in Tissue Repair, Drug Discovery and Immune Modulation
Current Drug Delivery A New Method to Measure P-gp (ABCB1) Activity
Drug Metabolism Letters