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
-
SUMOylation Modulates CFTR Biogenesis: Is the Pathway Druggable?
Current Drug Targets Polymer Drug Conjugates: Recent Advancements in Various Diseases
Current Pharmaceutical Design Utilising Nanotechnology and Nanosystems for Treatment of Rare Diseases
Pharmaceutical Nanotechnology Bone-Targeted Doxorubicin-Loaded Nanoparticles as a Tool for the Treatment of Skeletal Metastases
Current Cancer Drug Targets Retinoid Related Molecules an Emerging Class of Apoptotic Agents with Promising Therapeutic Potential in Oncology: Pharmacological Activity and Mechanisms of Action
Current Pharmaceutical Design Ligand Binding Domain of Vitamin D Receptors
Current Topics in Medicinal Chemistry Tankyrases: Structure, Function and Therapeutic Implications in Cancer
Current Pharmaceutical Design 5-Lipoxygenase and Cyclooxygenase Inhibitory Dammarane Triterpenoid 1 from Borassus flabellifer Seed Coat Inhibits Tumor Necrosis Factor-α Secretion in LPSInduced THP-1 Human Monocytes and Induces Apoptosis in MIA PaCa-2 Pancreatic Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry Mechanisms Controlling Sensitivity to Platinum Complexes: Role of p53 and DNA Mismatch Repair
Current Cancer Drug Targets Identification of AHSA1 as a Potential Therapeutic Target for Breast Cancer: Bioinformatics Analysis and <i>in vitro</i> Studies
Current Cancer Drug Targets The Cross-over of Anticancer Agents with Osteoclast Activities
Current Cancer Therapy Reviews Perspectives in Breast and Ovarian Cancer Chemotherapy by Nanomedicine Approach: Nanoformulations in Clinical Research
Current Medicinal Chemistry Repurposing of Anticancer Drugs for the Treatment of Bacterial Infections
Current Topics in Medicinal Chemistry Targeting Interleukin-1β for Pain
CNS & Neurological Disorders - Drug Targets Potentiation of Anti-Cancer Treatment by Modulators of Energy Metabolism
Current Pharmaceutical Biotechnology Recent Advances in Copper Radiopharmaceuticals
Current Radiopharmaceuticals Resveratrol in Medicinal Chemistry: A Critical Review of its Pharmacokinetics, Drug-Delivery, and Membrane Interactions
Current Medicinal Chemistry Focus on MicroRNAs as Biomarker in Pediatric Diseases
Current Pharmaceutical Design Regulation and Importance of the PI3K/Akt/mTOR Signaling Pathway in Hematologic Malignancies
Anti-Cancer Agents in Medicinal Chemistry Impact of Magnetic Nanoparticles in Biomedical Applications
Recent Patents on Drug Delivery & Formulation