Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-12-7
pubmed:abstractText
We studied the effects of ICI 182780 and bis(ethyl)norspermine (BE-3-3-3) on cell growth and apoptosis of estrogen receptor-positive MCF-7 breast cancer cells. Combination treatment with 100 nM ICI 182780 and 5 microM BE-3-3-3 for 6 days inhibited cell growth by 74.3+/-8.4% in MCF-7 cells, compared to that of 25.4+/-5.8 and 45.8+/-12.2%, respectively, when ICI 182780 and BE-3-3-3 were used as single agents. Treatment with 100 nM ICI 182780 and 5 microM BE-3-3-3 as single agents resulted in 9.1+/-1.0% and 35.1+/-4.5% apoptosis, respectively, as measured by APO-BRDU assay. When ICI 182780 and BE-3-3-3 were used in combination, the percentage of apoptosis was 60.6+/-3.8%. Improved efficacy of ICI 182780 and BE-3-3-3 combination on growth inhibition was observed for T-47D cells also. Western blot analysis showed that combinations of ICI 182780 and BE-3-3-3 caused down-regulation of the anti-apoptotic Bcl-2 and Bcl-XL proteins and increased the level of the pro-apoptotic Bax protein. Combination treatment also increased caspase-8 activation. Analysis of polyamine levels 48 h after combination treatment showed that spermidine and spermine levels were down regulated significantly. These studies indicate a potentially effective combination strategy for breast cancer treatment. Our results also link the down-regulation of polyamine pathway to apoptotic cell death and regulation of mediators of cell death.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1021-335X
pubmed:author
pubmed:issnType
Print
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
101-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Bis(ethyl)norspermine potentiates the apoptotic activity of the pure antiestrogen ICI 182780 in breast cancer cells.
pubmed:affiliation
Department of Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't