Linked Life Data

20721970

Source:http://linkedlifedata.com/resource/pubmed/id/20721970

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2010-9-22
pubmed:abstractText
Prostate cancer (PCA) is the second most malignancy in American men. Advanced stage PCA cells possess unlimited replication potential as well as resistance to apoptosis. Therefore, targeting survival mechanisms and activating apoptotic machinery in PCA cells using nontoxic phytochemicals is suggested as an attractive strategy against this deadly malignancy. In the present study, we assessed the effect of one such botanical agent, namely isosilybin A, on apoptotic machinery and key members of cell survival signaling [Akt, NF-?B, and androgen receptor (AR)] in different PCA cells. Results showed that isosilybin A (90-180?µM) treatment significantly induces apoptotic death by activating both extrinsic (increased level of DR5 and cleaved caspase 8) and intrinsic pathways (caspase 9 and 3 activation) of apoptosis in three different human PCA cell lines namely 22Rv1, LAPC4, and LNCaP. Further, isosilybin A treatment decreased the levels of phospho-Akt (serine-473), total Akt, and the nuclear levels of NF-?B constituents (p50 and p65). Isosilybin A treatment also decreased the AR and PSA level in 22Rv1, LAPC4, and LNCaP cells. Employing pan-caspase inhibitor (Z-VAD.fmk), we confirmed that isosilybin A-mediated decreased AR is independent of caspases activation. Temporal kinetics analysis showed that the primary effect of isosilybin A is on AR, as decrease in AR was evident much earlier (4?h) relative to caspase activation and apoptosis induction (12?h). Overall, our results demonstrated that isosilybin A activates apoptotic machinery in PCA cells via targeting Akt-NF-?B-AR axis; thereby, indicating a promising role for this phytochemical in the management of clinical PCA.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1098-2744
pubmed:author
pubmed:copyrightInfo
© 2010 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
902-12
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Isosilybin A induces apoptosis in human prostate cancer cells via targeting Akt, NF-?B, and androgen receptor signaling.
pubmed:affiliation
Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Denver, Aurora, Colorado, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural