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
-
Urokinase-a Very Popular Cardiovascular Agent
Recent Patents on Cardiovascular Drug Discovery Radioimmunotherapy of Solid Tumors: Searching for the Right Target
Current Drug Delivery The mTOR/4E-BP1/eIF4E Signalling Pathway as a Source of Cancer Drug Targets
Current Medicinal Chemistry Methylenetetrahydrofolate Reductase (MTHFR): A Novel Target for Cancer Therapy
Current Pharmaceutical Design Reprofiling of Troglitazone Towards More Active and Less Toxic Derivatives: A New Hope for Cancer Treatment?
Current Topics in Medicinal Chemistry Effects of Specific Cyclooxygenase-2 Inhibitors on Carcinogenesis
Medicinal Chemistry Reviews - Online (Discontinued) Current Molecularly Targeting Therapies in NSCLC and Melanoma
Anti-Cancer Agents in Medicinal Chemistry Drug Targets to Pro-Angiogenetic Factors with Special Reference to Primary Peritoneal Mesothelioma
Endocrine, Metabolic & Immune Disorders - Drug Targets The Need for Diagnostic Criteria in Systemic Vasculitis
Current Immunology Reviews (Discontinued) Antibody-Onconase Conjugates: Cytotoxicity and Intracellular Routing
Current Pharmaceutical Biotechnology Drug Delivery Systems for Brain Tumor Therapy
Current Pharmaceutical Design Activated Cancer Therapy Using Light and Ultrasound - A Case Series of Sonodynamic Photodynamic Therapy in 115 Patients Over a 4 Year Period
Current Drug Therapy Novel Marine-Derived Anti-Cancer Agents
Current Pharmaceutical Design Activity of Drug-loaded Tumor-Penetrating Microparticles In Peritoneal Pancreatic Tumors
Current Cancer Drug Targets Natural Products in Structure-Assisted Design of Molecular Cancer Therapeutics
Current Pharmaceutical Design Metabolic Targeting of Cancers: From Molecular Mechanisms to Therapeutic Strategies
Current Medicinal Chemistry Metastasis Suppressors: Basic and Translational Advances
Current Pharmaceutical Biotechnology Potential Utilization of Bystander / Abscopal-Mediated Signal Transduction Events in the Treatment of Solid Tumors
Current Signal Transduction Therapy Nucleic Acid-Based Aptamers: Applications, Development and Clinical Trials
Current Medicinal Chemistry Melanoma
Current Cancer Therapy Reviews