Abstract
Malignant pleural mesothelioma (MPM) is a lethal disease with scarce therapeutic options, and preclinical studies on new targeted-agents are warranted. Because previous studies reported high c-Met expression and alterations in the microtubules network in most MPM samples, we evaluated the activity of tivantinib, which has been recently suggested to affect microtubule polymerization in addition to inhibiting c-Met. In four MPM cell lines tivantinib inhibited both c-Met activity and microtubule polymerization, resulting in inhibition of cell-growth with IC50s ranging between 0.3 µM (MSTO-211H) and 2.4 µM (H2052). Furthermore tivantinib synergistically enhanced the antiproliferative and proapoptotic activity of pemetrexed, as detected by sulforhodamine-B-assay and flow cytometry. The synergistic interaction was associated with reduction of thymidylate synthase expression and inhibition of migratory activity. In aggregate, these data show the ability of tivantinib to specifically target key pathways in MPM cells and synergistically interact with pemetrexed, supporting further studies on this therapeutic approach.
Keywords: c-Met, malignant pleural mesothelioma, migration, pemetrexed, synergistic interaction, tivantinib, tubulin.
Current Drug Targets
Title:Synergistic Activity of the c-Met and Tubulin Inhibitor Tivantinib (ARQ197) with Pemetrexed in Mesothelioma Cells
Volume: 15 Issue: 14
Author(s): Leticia G. Leon, Maria Gemelli, Rocco Sciarrillo, Amir Avan, Niccola Funel and Elisa Giovannetti
Affiliation:
Keywords: c-Met, malignant pleural mesothelioma, migration, pemetrexed, synergistic interaction, tivantinib, tubulin.
Abstract: Malignant pleural mesothelioma (MPM) is a lethal disease with scarce therapeutic options, and preclinical studies on new targeted-agents are warranted. Because previous studies reported high c-Met expression and alterations in the microtubules network in most MPM samples, we evaluated the activity of tivantinib, which has been recently suggested to affect microtubule polymerization in addition to inhibiting c-Met. In four MPM cell lines tivantinib inhibited both c-Met activity and microtubule polymerization, resulting in inhibition of cell-growth with IC50s ranging between 0.3 µM (MSTO-211H) and 2.4 µM (H2052). Furthermore tivantinib synergistically enhanced the antiproliferative and proapoptotic activity of pemetrexed, as detected by sulforhodamine-B-assay and flow cytometry. The synergistic interaction was associated with reduction of thymidylate synthase expression and inhibition of migratory activity. In aggregate, these data show the ability of tivantinib to specifically target key pathways in MPM cells and synergistically interact with pemetrexed, supporting further studies on this therapeutic approach.
Export Options
About this article
Cite this article as:
Leon G. Leticia, Gemelli Maria, Sciarrillo Rocco, Avan Amir, Funel Niccola and Giovannetti Elisa, Synergistic Activity of the c-Met and Tubulin Inhibitor Tivantinib (ARQ197) with Pemetrexed in Mesothelioma Cells, Current Drug Targets 2014; 15 (14) . https://dx.doi.org/10.2174/1389450116666141205160924
DOI https://dx.doi.org/10.2174/1389450116666141205160924 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
New drug therapy for eye diseases
Eyesight is one of the most critical senses, accounting for over 80% of our perceptions. Our quality of life might be significantly affected by eye disease, including glaucoma, diabetic retinopathy, dry eye, etc. Although the development of microinvasive ocular surgery reduces surgical complications and improves overall outcomes, medication therapy is ...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
-
Points of Therapeutic Intervention Along the Wnt Signaling Pathway in Hepatocellular Carcinoma
Anti-Cancer Agents in Medicinal Chemistry Mitocans: Mitochondrial Targeted Anti-Cancer Drugs as Improved Therapies and Related Patent Documents
Recent Patents on Anti-Cancer Drug Discovery Nanoparticles Mediated Target-specific Drug Delivery in Prostate Cancer: An In-depth Review
Current Medicinal Chemistry Validated RP-HPLC Method for the Simultaneous Analysis of Gemcitabine and LY-364947 in Liposomal Formulations
Current Drug Targets Recent Patents on Light Based Therapies: Photodynamic Therapy, Photothermal Therapy and Photoimmunotherapy
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Oxytocin - A Multifunctional Analgesic for Chronic Deep Tissue Pain
Current Pharmaceutical Design Prognostic and Therapeutic Implications of MicroRNA in Malignant Pleural Mesothelioma
MicroRNA Antisense Therapy for Cardiovascular Diseases
Current Pharmaceutical Design Biosystems Engineering of Prokaryotes with Tumor-Killing Capacities
Current Pharmaceutical Design Synthesis and Antiproliferative Activity of Substituted 3[2-(1H-indol-3-yl)- 1,3-thiazol-4-yl]-1H-pyrrolo[3,2-b]pyridines, Marine Alkaloid Nortopsentin Analogues
Current Medicinal Chemistry The Role of Systemic Treatment and Radiotherapy in Malignant Mesothelioma
Current Respiratory Medicine Reviews Platinum-Based Agents for Individualized Cancer Treatment
Current Molecular Medicine An Interventional Pulmonologist’s Tool: Endobronchial Ultrasound- Guided Transbronchial Needle Aspiration (EBUS-TBNA) in Thoracic Disease — An Update
Current Respiratory Medicine Reviews Will Antiangiogenic Agents be a Future for Mesothelioma Therapy?
Current Medicinal Chemistry Screening of Drug Efficacy of Rosmarinic Acid Derivatives as Aurora Kinase Inhibitors by Computer-Aided Drug Design Method
Current Computer-Aided Drug Design Regulation and Quantification of Cellular Mitochondrial Morphology and Content
Current Pharmaceutical Design MDA-7/IL-24-Based Cancer Gene Therapy: Translation from the Laboratory to the Clinic
Current Gene Therapy Combining Oncolytic Virotherapy and Cytotoxic Therapies to Fight Cancer
Current Pharmaceutical Design A Review on Clinical Management and Pharmacological Therapy on Hereditary Haemorrhagic Telangiectasia (HHT)
Current Vascular Pharmacology Pulmonary Surfactant Proteins A and D: Innate Immune Functions and Biomarkers for Lung Diseases
Current Pharmaceutical Design