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
-
Update on the Rheumatologic Manifestations of Malignancy
Current Cancer Therapy Reviews Reprogrammed Metabolism of Cancer Cells as a Potential Therapeutic Target
Current Pharmaceutical Design Organoselenium Compounds in Cancer Chemoprevention
Mini-Reviews in Medicinal Chemistry The Ubiquitin-Proteasome System (UPS) and the Mechanism of Action of Bortezomib
Current Pharmaceutical Design Targeting Drugs Against Fibroblast Growth Factor(s)-Induced Cell Signaling
Current Drug Targets New Indications for Established Drugs: Combined Tumor-Stroma-Targeted Cancer Therapy with PPARγ Agonists, COX-2 Inhibitors, mTOR Antagonists and Metronomic Chemotherapy
Current Cancer Drug Targets Targeting Neuronal Nicotinic Receptors in Cancer: New Ligands and Potential Side-Effects
Recent Patents on Anti-Cancer Drug Discovery Neurochemical Markers in the Mammalian Brain: Structure, Roles in Synaptic Communication, and Pharmacological Relevance
Current Medicinal Chemistry 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 Therapeutic Strategies for Targeting BRAF in Human Cancer
Reviews on Recent Clinical Trials Tamoxifen and its New Derivatives in Cancer Research
Recent Patents on Anti-Cancer Drug Discovery Editorial (Thematic Issue: Novel Pharmaceutical Approaches by Natural Compound-Derived Epigenetic Regulators: Epigenetic Readers, Writers and Erasers as Therapeutic Targets)
Current Topics in Medicinal Chemistry Comparative Proteomics and Bioinformatics Analysis of Tissue from Non-Small Cell Lung Cancer Patients
Current Proteomics Amino Acid Degrading Enzymes and their Application in Cancer Therapy
Current Medicinal Chemistry The Cell-Type Specificity and Endosomal Escape of Cell-Penetrating Peptides
Current Pharmaceutical Design Carbon Nanotubes in the Diagnosis and Treatment of Malignant Melanoma
Anti-Cancer Agents in Medicinal Chemistry The Ubiquitin-Proteasome System as a Prospective Molecular Target for Cancer Treatment and Prevention
Current Protein & Peptide Science HGF Airway Over-expression Leads to Enhanced Pulmonary Vascularization without Induction of VEGF
Current Angiogenesis (Discontinued) The Role of CD40 Expression in Dendritic Cells in Cancer Biology; A Systematic Review
Current Cancer Drug Targets The Chemistry and Bio-Medicinal Significance of Pyrimidines & Condensed Pyrimidines
Current Topics in Medicinal Chemistry