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.
Related Journals
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry
Current Analytical Chemistry
Current Computer-Aided Drug Design
Current Bioactive Compounds
Current Cancer Drug Targets
Combinatorial Chemistry & High Throughput Screening
Current Cancer Therapy Reviews
Current Diabetes Reviews
Current Drug Safety
Current Drug Targets
Related Books
test ebook
2-Deoxy-D-Glucose: Chemistry and Biology
Chiral Ionic Liquids: Applications in Chemistry and Technology
Anthocyanins: Pharmacology and Nutraceutical Importance
Therapeutic Insights into Herbal Medicine through the Use of Phytomolecules
Computer-Aided Drug Discovery Methods: A Brief Introduction
The Roles and Responsibilities of Clinical Pharmacists in Hospital Settings
Bioactive Compounds from Medicinal Plants for Cancer Therapy and Chemoprevention
Biochar - Solid Carbon for Sustainable Agriculture
DFT-Based Studies On Atomic Clusters
27