Linked Life Data

8417823

Source:http://linkedlifedata.com/resource/pubmed/id/8417823

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1993-2-3
pubmed:abstractText
Many breast tumors are hormone dependent, and there is evidence that hydrolysis of estrone sulfate (E1S) to estrone, by estrone sulfatase, is an important source of the estrogen which is found in tumors. In this study, we have developed a novel pathway for the synthesis of estrone-3-methylthiophosphonate (E1-3-MTP) and examined its ability to inhibit estrone sulfatase activity in MCF-7 breast cancer cells and human placental and breast tumor preparations. In MCF-7 breast cancer cells, E1-3-MTP, 100 nM and 10 microM, inhibited estrone sulfatase activity by 52 and > 98%, respectively. The apparent Km and Vmax for E1S were 4.8 microM and 148 pmol/min/mg for placental and 16.9 microM and 38 pmol/min/mg for breast tumor preparations. Kinetic studies revealed that E1-3-MTP inhibited estrone sulfatase in a competitive manner with the Ki values for placental and tumor preparations being 14.6 and 32.8 microM, respectively. A comparison of the metabolism of [3H]E1S and [3H]E1-3-MTP by human placenta or rat liver revealed that, whereas 50-60% of [3H]E1S was converted to [3H]estrone, < 3% of [3H]E1-3-MTP was hydrolyzed. The development of an efficient inhibitor of estrone sulfatase, which is resistant to metabolism, will allow the importance of the estrone sulfatase pathway of estrogen formation in breast tumors to be assessed and such an inhibitor may have considerable potential as a therapeutic agent.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
53
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
298-303
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Inhibition of estrone sulfatase activity by estrone-3-methylthiophosphonate: a potential therapeutic agent in breast cancer.
pubmed:affiliation
Unit of Metabolic Medicine, St. Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, London, United Kingdom.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't