ALL libraries (COBIB.SI union bibliographic/catalogue database)
13.
Biochemical and biological evaluation of novel potent coumarin inhibitor of 17ß-HSD type 1
Starčević, Štefan ...
Human 17beta-hydroxysteroid dehydrogenase (17beta-HSD) type 1 is an enzyme that acts at the pre-receptor level. It catalyzes the NADPH-dependent reduction of the weak estrogen estrone into the most ...potent estrogen 17beta-estradiol, which exerts proliferative effects via estrogen receptors. Overexpression of 17beta-HSD type 1 in estrogen-responsive tissues is related to the development of hormone-dependent diseases, such as breast cancer and endometriosis. 17beta-HSD type 1 thus represents an attractive target for development of new drugs. Recently, we discovered that substituted coumarin derivatives potently and selectively inhibit 17beta-HSD type 1. In the presentstudy, we have performed additional biochemical and biological evaluation of the most promising coumarin derivative. First, we used an efficient method for isolation and purification of the active, soluble recombinant human 17beta-HSD type 1 from Escherichia coli. This 17beta-HSD type 1 showed a specific activity of 0.64+/-0.08mumolmin(-1)mg(-1) for estronereduction in the presence of NADPH at pH 6.5, and a K(m) of 62nM for estrone. Next, we evaluated the best of the coumarin-derivative inhibitors, showing its reversible and competitive inhibition of 17beta-HSD type 1 reductive activity with a K(i) of 53nM. We confirmed that this coumarin inhibitor acts not only in a cell-free assay, but also decreases endogenous 17beta-HSD type 1 activity in human T-47D breast cancer cells. This inhibitor also reduced estrone dependent growth of T-47D cells after 48h of incubation.
It was not necessary to add the material to the shelf.
Bibliographic material was successfully added on shelf.
Adding bibliographical material on shelf was not successful.
Material is already on the shelf.
Permalink
URL:
Impact factor
Access to the JCR database is permitted only to users from Slovenia. Your current IP address is not on the list of IP addresses with access permission, and authentication with the relevant AAI accout is required.
Year
Impact factor
Edition
Category
Classification
JCR
SNIP
JCR
SNIP
JCR
SNIP
JCR
SNIP
Select the library membership card:
DRS,
in which the journal is indexed
Database name
Field
Year
Links to authors' personal bibliographies
Links to information on researchers in the SICRIS system
Subject headings in COBISS General List of Subject Headings
Select pickup location
The material from the parent unit is free. If the material is delivered to the pickup location from another unit, the library may charge you for this service.
