Linked Life Data

16502348

Source:http://linkedlifedata.com/resource/pubmed/id/16502348

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2006-6-9
pubmed:abstractText
Acyloxyalkyl ester prodrugs of histone deacetylase inhibitors, a family of anti-cancer agents, are metabolized intracellularly to acids and aldehyde(s). The purpose of this study was to assess the in vitro and in vivo anticancer activity, selectivity and oral bioavailability of these prodrugs. The prodrugs exhibited a hierarchal potency of AN-193 > or = AN-7 > AN-1 and AN-9 >> AN-10 against murine lung carcinoma (3LLD122) and human breast carcinoma (MCF-7) cell lines. AN-9, and to even greater extent AN-7, displayed preferential cytotoxicity against leukemic and glioblastoma cells compared to their normal cellular counterparts-normal mononuclear and astrocytes cells, respectively. In vivo, anti-metastatic activity was evaluated in a metastatic model of lung cancer in which Lewis lung carcinoma (3LLD122) cells are injected intravenously into C57/BL mice and produce lung nodules. The prodrugs administered orally demonstrated a significant inhibition of lung-lesion formation and their hierarchal potency concurred with that observed in vitro, with the exception of AN-193 that was the least active compound. Escalating doses of AN-7 (5-100 mg/kg), administered by oral or intraperitoneal routes and displayed equivalent anti-metastatic activities, confirmed the good oral bioavailability of AN-7. Consistent with these findings, a time course study of histone acetylation in subcutaneously implanted 3LL122 tumors showed 2-4 fold increases in histone acetylation within 0.5 h of intravenous, intraperitoneal, or oral administration of AN-7 (100 mg/kg). Relative contributions of the prodrug metabolites to the anti-neoplastic activity and the best candidate for clinical studies are discussed.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0167-6997
pubmed:author
pubmed:issnType
Print
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
383-92
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16502348-Acetylation, pubmed-meshheading:16502348-Administration, Oral, pubmed-meshheading:16502348-Animals, pubmed-meshheading:16502348-Antineoplastic Agents, pubmed-meshheading:16502348-Biological Availability, pubmed-meshheading:16502348-Butyrates, pubmed-meshheading:16502348-Carcinoma, Lewis Lung, pubmed-meshheading:16502348-Cell Line, Tumor, pubmed-meshheading:16502348-Cell Proliferation, pubmed-meshheading:16502348-Enzyme Inhibitors, pubmed-meshheading:16502348-Female, pubmed-meshheading:16502348-Histone Deacetylase Inhibitors, pubmed-meshheading:16502348-Histones, pubmed-meshheading:16502348-Humans, pubmed-meshheading:16502348-Injections, Intraperitoneal, pubmed-meshheading:16502348-Leukocytes, Mononuclear, pubmed-meshheading:16502348-Lung, pubmed-meshheading:16502348-Mice, pubmed-meshheading:16502348-Mice, Inbred C57BL, pubmed-meshheading:16502348-Neoplasm Transplantation, pubmed-meshheading:16502348-Prodrugs
pubmed:year
2006
pubmed:articleTitle
The selectivty and anti-metastatic activity of oral bioavailable butyric acid prodrugs.
pubmed:affiliation
Felsenstein Medical Research Center, Sackler School of Medicine, Tel Aviv University, Beilinson Campus, Petach Tikva, 49100, Israel.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural