The insect repellent N,N-diethyl-m-toluamide (DEET) induces angio | 54488
Journal of Clinical Toxicology

Journal of Clinical Toxicology
Open Access

ISSN: 2161-0495

The insect repellent N,N-diethyl-m-toluamide (DEET) induces angiogenesis via allosteric modulation of the M3 muscarinic receptor in endothelial cells

7th Euro-Global Summit on Toxicology & Applied Pharmacology

October 24-26, 2016 Rome, Italy

Samuel Legeay

University of Angers, France

Scientific Tracks Abstracts: J Clin Toxicol

Abstract :

The insect repellent N,N-diethyl-m-toluamide (DEET) has been reported to inhibit AChE (acetylcholinesterase) and to be associated with increased risk of cancer. In the present paper, we demonstrate that DEET specifically stimulates endothelial cells that promote angiogenesis which increases tumor growth in vivo. DEET activates cellular processes that lead to angiogenesis including proliferation, migration and adhesion. This is associated with an enhancement of NO production and VEGF expression in endothelial cells. M3 silencing or the use of a pharmacological M3 inhibitor abrogates all of these effects which reveals that DEET-induced angiogenesis is M3 sensitive. The experiments involving calcium signals in both endothelial and HEK cells overexpressing M3 receptors, as well as binding and docking studies demonstrate that DEET acts as an allosteric modulator of the M3 receptor. In addition, DEET inhibited AChE which increased acetylcholine bioavailability and binding to M3 receptors and also strengthened pro-angiogenic effects by an allosteric modulation.

Biography :

Samuel Legeay is a PharmD PhD student at the University of Angers in France (west part of France). He worked mainly on two different subjects: In USA at Augusta University (Georgia) on the regulation of hypertension in diabetic conditions and at the University of Angers (France) on the impact of mosquito repellents in angiogenesis. He has 2 published articles in PubMed and 1 book chapter and is a member of the French Society of Pharmacology and Therapeutics.