Linked Life Data

18575740

Source:http://linkedlifedata.com/resource/pubmed/id/18575740

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-6-25
pubmed:abstractText
Histone deacetylase inhibitors (HDIs) as well as non-steroidal anti-inflammatory drugs including aspirin show promise as antineoplastic agents. The treatment with both HDIs and aspirin can result in hyperacetylation of proteins. In this study, we investigated whether HDIs and aspirin interacted in inducing anticancer activity and histone acetylation. We found that the HDIs, suberoylanilide hydroxamic acid and sodium butyrate, and aspirin cooperated to induce cell death in the ovarian cancer cell line, A2780. The effect was synergistic, as evidenced by CI-isobologram analysis. However, aspirin had no effect on histone acetylation, neither in the absence nor presence of HDIs. To gain insight into the mechanism underlying the synergistic action of HDIs and aspirin, we employed the deacetylated metabolite of aspirin, salicylic acid, and the cyclooxygenase-1- and -2-selective inhibitors, SC-560 and NS-398, respectively. We found that HDIs and salicylic acid interacted synergistically, albeit less efficiently than HDIs and aspirin, to induce cancer cell death, suggesting that the acetyl and the salicyl moiety contributed to the cooperative interaction of aspirin with HDIs. SC-560 and NS-398 had little effect both when applied alone or in conjunction with HDIs, indicating that the combinatorial effect of HDIs and aspirin was not the result of cyclo-oxygenase inhibition. In conclusion, our study demonstrates that HDIs and aspirin synergize to induce cancer cell death and, thus, provides a rationale for a more in-depth exploration into the potential of combining HDIs and aspirin as a strategy for anticancer therapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1021-335X
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
219-24
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Histone deacetylase inhibitors and aspirin interact synergistically to induce cell death in ovarian cancer cells.
pubmed:affiliation
University Children's Hospital Jena, D-07743 Jena, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't