Linked Life Data

19007764

Source:http://linkedlifedata.com/resource/pubmed/id/19007764

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-3
pubmed:dateCreated
2009-2-9
pubmed:abstractText
AKR1C3 (also known as 17beta-hydroxysteroid dehydrogenase type 5 or 3alpha-hydroxysteroid dehydrogenase type 2) functions as a 3-keto, 17-keto and 20-ketosteroid reductase and as a 3alpha-, 17beta- and 20alpha-hydroxysteroid oxidase. Relatively high mRNA expression of AKR1C3 was found in human prostate and mammary gland where it is implicated in regulating ligand access to the androgen and estrogen receptor, respectively. AKR1C3 is an interesting target for the development of agents for treating hormone-dependent forms of cancer like prostate cancer, breast cancer, and endometrial cancer. However, only a few clinically promising and selective inhibitors have been reported so far. Very potent inhibitors of AKR1C3 are the non-steroidal anti-inflammatory drugs, e.g. indomethacin or flufenamic acid. Also dietary phytoestrogens such as coumestrol, quercetin, and biochanin were reported to inhibit the enzyme in low micromolar concentrations. In this study, some dietary flavonoids and other phenolic compounds were tested for their ability to specifically inhibit AKR1C3. Carbonyl reduction of the anticancer drug oracin, which is a very good substrate for AKR1C3 and which could be well monitored by a sensitive HPLC system with fluorescence detection, was employed to determine the inhibitory potency of the compounds. Our results reveal that AKR1C3 could be potentially un-competitively inhibited by 2'-hydroxyflavanone, whose IC(50) value of 300nM is clinically promising. Moreover, since the inhibition is selective towards AKR1C3, 2'-hydroxyflavanone could be useful for treating or preventing hormone-dependent malignancies like prostate and breast cancer.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1872-7786
pubmed:author
pubmed:issnType
Electronic
pubmed:day
16
pubmed:volume
178
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
138-44
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
AKR1C3 as a potential target for the inhibitory effect of dietary flavonoids.
pubmed:affiliation
Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't