Linked Life Data

16865282

Source:http://linkedlifedata.com/resource/pubmed/id/16865282

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2006-7-25
pubmed:abstractText
Calpain is a class of Ca(2+)-dependent cysteine proteases and has been suggested to be involved in several important signaling cascades. A series of novel aldehyde calpain inhibitors identified in our laboratory were more potent and specific than commercially available calpain inhibitors, and were used to assess the involvement of calpain in cancer. Our inhibitors demonstrated potent anti-proliferative activity in four cancer cell lines (PC-3, HeLa, Jurkat and Daudi) with IC(50)'s ranging from 2 to >30 microM. A non-cancer cell line (CV-1) was 4-7-fold less sensitive than the cancer cell lines. Apoptotic activity was determined and appeared to be inversely correlated to calpain expression levels in the different cell types. Leukemia cell lines (i.e., Daudi and Jurkat) with undetectable m-calpain were more susceptible to the apoptotic effects in response to calpain inhibition, while apoptosis was not detected in PC-3 prostate cancer cells, which highly express m-calpain. The extent of apoptosis in HeLa cells was moderate under identical conditions. Apoptosis induced by calpain inhibition was accompanied by caspase-3 activation. Furthermore, cell cycle analysis showed that aldehyde calpain inhibitors arrested cells at the G2/M boundary in a concentration-dependent manner. These results indicate that aldehyde calpain inhibitors exhibit their cytotoxic effects via induction of G2/M arrest and apoptosis. Importantly, the compounds failed to exert any inhibitory effects toward 20S proteasome. Collectively, our results suggest that calpain is a novel target for the treatment of a variety of cancer diseases and provide leads for further discovery and development of calpain inhibitors.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1019-6439
pubmed:author
pubmed:issnType
Print
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
655-63
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Apoptosis induced by novel aldehyde calpain inhibitors in human tumor cell lines.
pubmed:affiliation
Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, 43210, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural