Back to Search
Start Over
The potential endocrine disruption mechanism of anthelmintic drug niclosamide by activating estrogen receptors and estrogen-related receptors
- Source :
- Toxicology. 457:152805
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Niclosamide (NIC), a helminthic drug used widely for controlling schistosomiasis, can reportedly disrupt the endocrine system. However, its underlying mechanisms are still unclear. In this study, we revealed the potential endocrine disruption mechanism of NIC by activating estrogen receptors (ERs) and estrogen-related receptors (ERRs). The binding potency of NIC with ERα, ERβ and ERRγ were determined by fluorescence competitive binding assays, which shows an IC50 (the concentration of NIC needed to displace 50 % of the probe from the receptor) of 90 ± 4.1, 10 ± 1.7 nM and 0.59 ± 0.07 nM respectively. The IC50 for ERRγ is the lowest one among the three detected receptors, which is three orders of magnitude lower than the known agonist GSK4716.The transcriptional activities of NIC on ERs and ERRs were detected by MVLN cells (stably transfected with ERs reporter gene) and HeLa cells (transiently transfected with ERRs reporter gene)-based luciferase reporter gene assay. The lowest observable effective concentration (LOEC) ranked as follows: ERRγ (0.5 nM)
- Subjects :
- 0301 basic medicine
Agonist
medicine.drug_class
Estrogen receptor
Endocrine Disruptors
Pharmacology
Toxicology
Protein Structure, Secondary
HeLa
03 medical and health sciences
0302 clinical medicine
medicine
Estrogen Receptor beta
Humans
Receptor
IC50
Reporter gene
Dose-Response Relationship, Drug
biology
Chemistry
Estrogen Receptor alpha
Anticestodal Agents
Transfection
biology.organism_classification
030104 developmental biology
Receptors, Estrogen
Estrogen
MCF-7 Cells
Niclosamide
030217 neurology & neurosurgery
HeLa Cells
Protein Binding
Subjects
Details
- ISSN :
- 0300483X
- Volume :
- 457
- Database :
- OpenAIRE
- Journal :
- Toxicology
- Accession number :
- edsair.doi.dedup.....0a261c1a6f1d22af3d3ad5dc4d6fd371