Linked Life Data

9816181

Source:http://linkedlifedata.com/resource/pubmed/id/9816181

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1999-2-10
pubmed:abstractText
Phenylbutyrate (PB), a novel lead compound for prostate cancer therapy, has molecular activities distinct from its metabolite, phenylacetate (PA). Both PB and PA promote differentiation in human prostate cancer cell lines, yet little data exist comparing the cytotoxic effects of each drug. We found that PB is more potent than PA in vitro; PB is 1.5-2.5 times more active at inhibiting growth and inducing programmed cell death than PA at clinically achievable doses against each human prostate cancer line studied. PB is equipotent to sodium butyrate, which induces apoptosis and differentiation through multiple mechanisms. Exposure of prostate cancer cell lines to PB reduces their DNA synthesis, leads to fragmentation of genomic DNA, and causes 50-60% of cells to undergo apoptosis. These PB-induced effects are 2-10 times greater than those of the control or PA. The stereotypical changes of apoptosis can be seen with sodium butyrate at similar concentrations, but not with PA. Prostate cancer cell lines overexpressing P-glycoprotein or possessing heterogeneous molecular alterations, including p53 mutations, are also sensitive to the effects of PB. In vivo, Copenhagen rats treated with oral PB had delayed growth of the androgen refractory Dunning R-3327 MAT-LyLu prostate cancer subline by 30-45% in a dose-dependent manner. These results demonstrate that PB induces cytotoxicity via apoptosis in human prostate cancer, in addition to its differentiating properties.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1078-0432
pubmed:author
pubmed:issnType
Print
pubmed:volume
2
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
379-87
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Phenylbutyrate induces apoptosis in human prostate cancer and is more potent than phenylacetate.
pubmed:affiliation
The Johns Hopkins Oncology Center and The Brady Urological Institute, Baltimore, Maryland 21205, USA. carducci@welchlink.welch.jhu.edu
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.