Endothelin-converting enzyme-1 inhibition and growth of human glioblastoma cells

Details

Ressource 1Request a copy Sous embargo indéterminé.
State: Public
Version: Final published version
License: All rights reserved
Serval ID
serval:BIB_9E6E325B5ABC
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Endothelin-converting enzyme-1 inhibition and growth of human glioblastoma cells
Journal
Journal of Medicinal Chemistry
Author(s)
Berger Y., Dehmlow H., Blum-Kaelin D., Kitas E. A., Loffler B. M., Aebi J. D., Juillerat-Jeanneret L.
ISSN
0022-2623 (Print)
Publication state
Published
Issued date
2005
Volume
48
Number
2
Pages
483-498
Language
english
Notes
PT - Journal Article PT - Research Support, Non-U.S. Gov't
Abstract
Endothelin-1 (ET-1) is mitogenic and/or antiapoptotic in human cancers, and antagonists to ET-1 receptors are under evaluation for cancer treatment. Inhibition of ET-1 activation by the endothelin-converting enzymes 1(a)(-)(d) (ECE-1(a)(-)(d); EC 3.4.24.71) represents another approach to block the ET-1 effect in cancer. To evaluate this potential, we synthesized and characterized a series of low nanomolar nonpeptidic thiol-containing ECE-1 inhibitors, and evaluated their effect, as well as the effect of inhibitors for the related metalloproteases neprilysin (NEP; EC 3.4.24.11) and angiotensin-converting enzyme (ACE; EC 3.4.15.1), on human glioblastoma cell growth. Only ECE-1 inhibitors inhibited DNA synthesis by human glioblastoma cells. Exogenous addition of ET-1 or bigET-1 to glioblastoma cells did not counterbalance the growth inhibition elicited by ECE-1 inhibitors, suggesting that ECE-1 inhibitors block the proliferation of human glioblastoma cells most likely via a mechanism not involving extracellular production of ET-1. This class of molecules may thus represent novel therapeutic agents for the potential treatment of human cancer
Keywords
Antineoplastic Agents/chemical synthesis/chemistry/pharmacology/Aspartic Endopeptidases/antagonists & inhibitors/Carbamates/Cell Line,Tumor/Cell Proliferation/drug effects/Central Nervous System Neoplasms/Drug Screening Assays,Antitumor/Endothelin-1/Glioblastoma/Humans/Hydrazines/Metalloendopeptidases/Proline/analogs & derivatives/Pyrimidines/Pyrrolidines/Structure-Activity Relationship/Sulfhydryl Compounds
Pubmed
Web of science
Create date
29/01/2008 19:35
Last modification date
14/07/2020 6:21
Usage data