Abstract
The present work describes the anticancer activity of a new indolylcoumarin named COUFIN and more specifically, its efficiency against clear cell renal carcinoma (CCRC). COUFIN inhibited microtubule formation and bound on tubulin to or near the colchicine site. In vitro, COUFIN showed potent anticancer activity on renal carcinoma cells (RCC) both in monolayer (2D culture) (IC50 of 88±8 nM) and multicellular tumor spheroid (3D culture) (IC50 of 180±20 nM). The compound blocked cell cycle transition at G2/M phase, induced a subsequent apoptotic process but did not modulate clonal growth of CFU-GM. On the other hand, the coumarin derivative decreased the activity of P-gp and BCRP but was not substrate for these ABC pumps. In vivo, the indolylcoumarin increased the survival rate after 3 weeks of treatment. Based on the present study, COUFIN was identified as a bifunctional molecule able to inhibit renal carcinoma cells proliferation without being effluxed by ABC proteins. Thus COUFIN could be a promising chemotherapeutic agent for treating tumor cells over-expressing efflux pumps and tumor cells irrigated by vessels lined with endothelial cells responsible of poor distribution of conventional anticancer agents.
Keywords: Apoptosis, Arylcoumarin, cancer, efflux pump, multidrug resistance, tubulin.
Anti-Cancer Agents in Medicinal Chemistry
Title:The Indolylcoumarin COUFIN Exhibits Potent Activity Against Renal Carcinoma Cells without Affecting Hematopoietic System
Volume: 14 Issue: 6
Author(s): Pierre Champelovier, Pascale Barbier, Etienne Daras, Soazig Douillard, Bertrand Toussaint, Virginie Persoon, Veronique Curri, Vincent Peyrot and Sebastien Combes
Affiliation:
Keywords: Apoptosis, Arylcoumarin, cancer, efflux pump, multidrug resistance, tubulin.
Abstract: The present work describes the anticancer activity of a new indolylcoumarin named COUFIN and more specifically, its efficiency against clear cell renal carcinoma (CCRC). COUFIN inhibited microtubule formation and bound on tubulin to or near the colchicine site. In vitro, COUFIN showed potent anticancer activity on renal carcinoma cells (RCC) both in monolayer (2D culture) (IC50 of 88±8 nM) and multicellular tumor spheroid (3D culture) (IC50 of 180±20 nM). The compound blocked cell cycle transition at G2/M phase, induced a subsequent apoptotic process but did not modulate clonal growth of CFU-GM. On the other hand, the coumarin derivative decreased the activity of P-gp and BCRP but was not substrate for these ABC pumps. In vivo, the indolylcoumarin increased the survival rate after 3 weeks of treatment. Based on the present study, COUFIN was identified as a bifunctional molecule able to inhibit renal carcinoma cells proliferation without being effluxed by ABC proteins. Thus COUFIN could be a promising chemotherapeutic agent for treating tumor cells over-expressing efflux pumps and tumor cells irrigated by vessels lined with endothelial cells responsible of poor distribution of conventional anticancer agents.
Export Options
About this article
Cite this article as:
Champelovier Pierre, Barbier Pascale, Daras Etienne, Douillard Soazig, Toussaint Bertrand, Persoon Virginie, Curri Veronique, Peyrot Vincent and Combes Sebastien, The Indolylcoumarin COUFIN Exhibits Potent Activity Against Renal Carcinoma Cells without Affecting Hematopoietic System, Anti-Cancer Agents in Medicinal Chemistry 2014; 14 (6) . https://dx.doi.org/10.2174/1871520614666140223190829
DOI https://dx.doi.org/10.2174/1871520614666140223190829 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
- 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
-
Adjuvant and Neoadjuvant Chemotherapy for Soft Tissue Sarcomas
Current Medicinal Chemistry Recent Advances in Characterizing Natural Products that Regulate Autophagy
Anti-Cancer Agents in Medicinal Chemistry Polymorphism in Endothelin-1 Gene: An Overview
Current Clinical Pharmacology Structure-Function Relationships of PEDF
Current Molecular Medicine Mining Sarcomas by Proteomics Approaches: Ewing Sarcoma on the Spotlight
Recent Patents on Biotechnology Cucurbitacin E, An Experimental Lead Triterpenoid with Anticancer, Immunomodulatory and Novel Effects Against Degenerative Diseases. A Mini-Review
Current Topics in Medicinal Chemistry MicroRNA-183 Functions As an Oncogene by Regulating PDCD4 in Gastric Cancer
Anti-Cancer Agents in Medicinal Chemistry Novel Mediators of Vitamin D Signaling in Cancer and Obesity
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Alternative Gene Therapy Strategies for the Repair of Craniofacial Bone Defects
Current Gene Therapy Phosphoinositide-3 Kinase Signaling in Cardiac Hypertrophy and Heart Failure
Current Pharmaceutical Design Protein-Protein Interaction Inhibitors: Small Molecules from Screening Techniques
Current Topics in Medicinal Chemistry Transductional and Transcriptional Targeting of Adenovirus for Clinical Applications
Current Gene Therapy Structure, Roles and Inhibitors of a Mitotic Protein Kinase Haspin
Current Medicinal Chemistry The S100A8 and S100A9 Proteins are Attractive Targets to Modulate Inflammation
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Carbon Nanotubes for Biomaterials in Contact with Bone
Current Medicinal Chemistry The Water Channels, New Druggable Targets to Combat Cancer Cell Survival,Invasiveness and Metastasis
Current Drug Targets Pharmacological Aspects of the Enzastaurin-Pemetrexed Combination in Non-Small Cell Lung Cancer (NSCLC)
Current Drug Targets Nanomedical Applications of Amphiphilic Dendrimeric Micelles
Current Medicinal Chemistry Mesenchymal Stem Cells in the Treatment of Amyotrophic Lateral Sclerosis
Current Stem Cell Research & Therapy Advances in the Use of Stem Cells and Tissue Engineering Applications in Bone Repair
Current Stem Cell Research & Therapy