Linked Life Data

10509759

Source:http://linkedlifedata.com/resource/pubmed/id/10509759

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1999-10-8
pubmed:abstractText
Didemnin B (DB) is one member of a class of natural cyclic depsipeptides that display potent cytotoxicity in vitro. The detailed mechanism of action of DB is unknown, although it appears to involve the inhibition of protein biosynthesis. Additional activities of DB have established DB as a rapid and potent inducer of apoptosis in HL-60 cells. Our aim was to determine if the induction of apoptosis by DB is mediated through inhibition of protein synthesis in MCF-7 human breast carcinoma cells. Apoptosis was observed only at > or = 100 nM DB, even though inhibition of protein synthesis occurred at much lower DB concentrations (IC50 = 12 nM). DB-induced apoptosis was mediated by caspase activation, since cleavage of the caspase substrate poly(ADPribose) polymerase was observed as early as 6 hr after DB exposure. Two additional protein synthesis inhibitors, cycloheximide (CHX) and emetine (ET), failed to induce apoptosis at concentrations that completely inhibited protein synthesis. Moreover, DB-induced apoptosis was enhanced only slightly by pre- and co-treatment with CHX and ET. Thus, inhibition of protein synthesis alone was not sufficient to induce apoptosis in these cells. As a measure of antiproliferative potential, DB (1-5 nM) inhibited the colony forming ability of MCF7 cells regardless of pretreatment with CHX. In conclusion, additional effects of DB, independent of protein synthesis inhibition, are proposed to account for its ability to induce apoptosis and prevent cell proliferation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
58
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1067-74
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Inhibition of protein synthesis by didemnin B is not sufficient to induce apoptosis in human mammary carcinoma (MCF7) cells.
pubmed:affiliation
Department of Internal Medicine and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor 48109-0946, USA. dbeidler@umich.edu
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.