Abstract
Background: Regardless of contemporary improvements in cancer treatment, the results of drug treatment are not always efficacious. Thus, the development of novel approaches that affect cancer cell-specific metabolic pathways is needed. Since much evidence has shown that tumor cell proliferation and motility are stimulated by glutamate via activation of its receptors, use of antagonists to these receptors may be the key to control cancer cell progression. Riluzole noncompetitive metabotropic glutamate receptor 1 (mGluR1) antagonist, commonly used to treat patients with amyotrophic lateral sclerosis (ALS), has shown some antineoplastic properties against melanoma, breast and prostate cancer. Yet little is known about its molecular mode of action.
Aims: The current study aims at evaluating the abilities of Riluzole to inhibit proliferation of several cancer cell lines, as well as resolve the mechanism of its action.
Method: We demonstrated antiproliferative and antimigrative properties of Riluzole in rhabdomyosarcomamedulloblastoma, neuroblastoma, astrocytoma, glioma, colon cancer, lung cancer, thyroid carcinoma, leukemia, erythroleukemia and multiple myeloma. Our studies revealed apoptosis induction and G2-M cell cycle arrest in Riluzole treated A549, C6 and HT-29 cells.
Result: At the molecular level, we found that these cells treated with Riluzole had a decrease of Cyclin B and an increase of p21 Waf1/Cip1 and p53 expression. We also observed an enhancement of CDK1 and Chk2 phosphorylation. Reported changes may suggest the involvement of these proteins in G2-M arrest, observed in flow cytometry analysis. These data indicated the potential use of Riluzole in the treatment of different types of cancers.
Keywords: Riluzole, proliferation, apoptosis, G2-M cell cycle arrest, migration, tumor.
Anti-Cancer Agents in Medicinal Chemistry
Title:Riluzole Inhibits Proliferation, Migration and Cell Cycle Progression and Induces Apoptosis in Tumor Cells of Various Origins
Volume: 18 Issue: 4
Author(s): Marta Kinga Lemieszek*, Andrzej Stepulak, Katarzyna Sawa-Wejksza, Arkadiusz Czerwonka, Chrysanthy Ikonomidou and Wojciech Rzeski
Affiliation:
- Department of Medical Biology, Institute of Agricultural Medicine, 20-090 Lublin,Poland
Keywords: Riluzole, proliferation, apoptosis, G2-M cell cycle arrest, migration, tumor.
Abstract: Background: Regardless of contemporary improvements in cancer treatment, the results of drug treatment are not always efficacious. Thus, the development of novel approaches that affect cancer cell-specific metabolic pathways is needed. Since much evidence has shown that tumor cell proliferation and motility are stimulated by glutamate via activation of its receptors, use of antagonists to these receptors may be the key to control cancer cell progression. Riluzole noncompetitive metabotropic glutamate receptor 1 (mGluR1) antagonist, commonly used to treat patients with amyotrophic lateral sclerosis (ALS), has shown some antineoplastic properties against melanoma, breast and prostate cancer. Yet little is known about its molecular mode of action.
Aims: The current study aims at evaluating the abilities of Riluzole to inhibit proliferation of several cancer cell lines, as well as resolve the mechanism of its action.
Method: We demonstrated antiproliferative and antimigrative properties of Riluzole in rhabdomyosarcomamedulloblastoma, neuroblastoma, astrocytoma, glioma, colon cancer, lung cancer, thyroid carcinoma, leukemia, erythroleukemia and multiple myeloma. Our studies revealed apoptosis induction and G2-M cell cycle arrest in Riluzole treated A549, C6 and HT-29 cells.
Result: At the molecular level, we found that these cells treated with Riluzole had a decrease of Cyclin B and an increase of p21 Waf1/Cip1 and p53 expression. We also observed an enhancement of CDK1 and Chk2 phosphorylation. Reported changes may suggest the involvement of these proteins in G2-M arrest, observed in flow cytometry analysis. These data indicated the potential use of Riluzole in the treatment of different types of cancers.
Export Options
About this article
Cite this article as:
Lemieszek Kinga Marta *, Stepulak Andrzej , Sawa-Wejksza Katarzyna , Czerwonka Arkadiusz , Ikonomidou Chrysanthy and Rzeski Wojciech , Riluzole Inhibits Proliferation, Migration and Cell Cycle Progression and Induces Apoptosis in Tumor Cells of Various Origins, Anti-Cancer Agents in Medicinal Chemistry 2018; 18 (4) . https://dx.doi.org/10.2174/1871520618666180228152713
DOI https://dx.doi.org/10.2174/1871520618666180228152713 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Discovery of Lead compounds targeting transcriptional regulation
Transcriptional regulation plays key physiological functions in body growth and development. Transcriptional dysregulation is one of the important biomarkers of tumor genesis and progression, which is involved in regulating tumor cell processes such as cell proliferation, differentiation, and apoptosis. Additionally, it plays a pivotal role in angiogenesis and promotes tumor ...read more
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 that aid in stabilizing chromosomal makeup. The resynthesis of telomeres is supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no telomerase activity in human somatic cells, but the stem cells and germ cells undergo ...read more
Innovative targets in medicinal chemistry
Medicinal chemistry continuously evolves in response to emerging healthcare needs and advancements in scientific understanding. This special issue explores the current landscape of innovative targets in medicinal chemistry, highlighting the quest for novel therapeutic avenues. From traditional drug targets such as enzymes and receptors to emerging targets like protein-protein interactions ...read more
Rechallenge Therapy in different types of cancer
Cancer is responsible for approximately 8 million deaths annually worldwide. GLOBOCAN 2020 reported 19.3 million new cases of cancer, which is projected to increase to 28.4 million by 2040. In the future, female breast cancer will be the most common cancer (11.7%), followed by lung (11.4%), colorectal (10.0%), prostate (7.3%), ...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
-
Advances in Photodynamic Therapy Assisted by Electroporation
Current Drug Metabolism Roles of TRAF6 in Central Nervous System
Current Neuropharmacology Human Skin-Derived Fibroblasts Acquire In Vitro Anti-Tumor Potential after Priming with Paclitaxel
Anti-Cancer Agents in Medicinal Chemistry Gemini Surfactant Based Carriers in Gene and Drug Delivery
Current Medicinal Chemistry Antineoplastic Activity, Structural Modification, Synthesis and Structure-activity Relationship of Dammarane-type Ginsenosides: An Overview
Current Organic Chemistry Development of Crystalline Cellulosic Fibres for Sustained Release of Drug
Current Topics in Medicinal Chemistry A Fluorescent Alkyllysophospholipid Analog Exhibits Selective Cytotoxicity Against the Hormone-Insensitive Prostate Cancer Cell Line PC3
Anti-Cancer Agents in Medicinal Chemistry Identification of Imidazoquinoline Derivatives as Potent Antiglioma Agents
Medicinal Chemistry Relationship with Programmed Cell Death Ligand 1 (PD-L1) and DTI Features in Brain Metastases of Non-small Cell Lung Cancer: A Preliminary Study
Current Medical Imaging Neurovascular Signals Suggest a Propagation Mechanism for Endogenous Stem Cell Activation Along Blood Vessels
CNS & Neurological Disorders - Drug Targets Combination Treatment of Glioblastoma by Low-Dose Radiation and Genistein
Current Radiopharmaceuticals Probucol Self-Emulsified Drug Delivery System: Stability Testing and Bioavailability Assessment in Human Volunteers
Current Drug Delivery Resveratrol Effects on Molecular Pathways and MicroRNAs in Gastrointestinal Cancers
Current Medicinal Chemistry Recent Advances on Antitumor Agents-loaded Polymeric and Lipid-based Nanocarriers for the Treatment of Brain Cancer
Current Pharmaceutical Design Chemical Composition and Biological Activities of <i>Croton delpyi, Croton decalvatus</i> and <i>Croton caudatus</i>
The Natural Products Journal MicroRNAs Used in Combination with Anti-Cancer Treatments Can Enhance Therapy Efficacy
Mini-Reviews in Medicinal Chemistry Effects of Plants and Isolates of Celastraceae Family on Cancer Pathways
Anti-Cancer Agents in Medicinal Chemistry Mitochondrial Physiology and Toxicity (Mitotoxicity); Importance for the Immune System, Programmed Cell Death and Cancer
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Radiofluorinated Carbohydrates for Positron Emission Tomography
Current Topics in Medicinal Chemistry Nanoparticle-based Drug Delivery Systems for Solid Brain Tumors
Current Nanoscience