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
-
Somatostatin, Somatostatin Analogs and Somatostatin Receptor Dynamics in the Biology of Cancer Progression
Current Molecular Medicine Clinical Applications and Biosafety of Human Adult Mesenchymal Stem Cells
Current Pharmaceutical Design Comparison of High-Density Short Oligonucleotide Microarray Platforms
Current Bioinformatics Metallic Nanoparticles as SERS Agents for Biomolecular Imaging
Current Pharmaceutical Biotechnology EDITORIAL [Hot Topic-I: Molecular and Pharmacological Aspects of Existing and Experimental Bone Anabolic Therapies (Guest Editor: Naibedya Chattopadhyay)]
Current Molecular Pharmacology Anticancer Mechanisms of Berberine: A Good Choice for Glioblastoma Multiforme Therapy
Current Medicinal Chemistry Potential Anticancer Properties of Bisphosphonates: Insights From Preclinical Studies
Anti-Cancer Agents in Medicinal Chemistry Histone Deacetylase Inhibitor Trichostatin A Suppresses Cell Proliferation and Induces Apoptosis by Regulating the PI3K/AKT Signalling Pathway in Gastric Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry Interplay between DNA Methyltransferase 1 and microRNAs During Tumorigenesis
Current Drug Targets Histone Modification in Osteogenic Differentiation of Skeletal Stem Cells
Current Stem Cell Research & Therapy The Interaction Between FAK, MYCN, p53 and Mdm2 in Neuroblastoma
Anti-Cancer Agents in Medicinal Chemistry Meet Our Editorial Board Member
Current Nanomedicine Diethyldithiocarbamate complex with copper: the mechanism of action in cancer cells
Mini-Reviews in Medicinal Chemistry Regulation and Function of DNA and Histone Methylations
Current Pharmaceutical Design The potential for circulating microRNAs in the diagnosis of myocardial infarction: a novel approach to disease diagnosis and treatment
Current Pharmaceutical Design Mechanism of Cancer Drug Resistance and the Involvement of Noncoding RNAs
Current Medicinal Chemistry The Efficacy of Vitamin K, A Member Of Naphthoquinones in the Treatment of Cancer: A Systematic Review and Meta-Analysis
Current Cancer Drug Targets Identification of Novel Anti-inflammatory Agents from Ayurvedic Medicine for Prevention of Chronic Diseases: “Reverse Pharmacology” and “Bedside to Bench” Approach
Current Drug Targets MicroRNA in Cervical Carcinogenesis: Window of Therapeutic Potential
Current Women`s Health Reviews Chelating Agents Used for Plutonium and Uranium Removal in Radiation Emergency Medicine
Current Medicinal Chemistry