Linked Life Data

18314260

Source:http://linkedlifedata.com/resource/pubmed/id/18314260

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-5-6
pubmed:abstractText
Recent studies indicate that gossypol possesses potent antitumor activities in vitro and in vivo. The nuclear factor-kappa B (NF-kappaB) plays an important role in tumor cell growth, proliferation, invasion, and survival. In this study, we investigated the effects and the molecular mechanisms of gossypol on NF-kappaB activation and NF-kappaB-related gene expression in human leukemia U937 cells. Treatment with concentrations of gossypol greater than 10 microM resulted in significant cell cytotoxicity and DNA fragmentation, indicative of apoptosis. Treatment with 10 microM gossypol also induced caspase-3 activation and poly(ADP-ribose)polymerase (PARP) cleavage, and resulted in the induction of apoptosis in approximately 20% of cells as determined by annexin-V staining 24h after treatment. Furthermore, gossypol exposure decreased the DNA-binding activity of NF-kappaB in a concentration-dependent manner. Treatment with gossypol also downregulated expression of NF-kappaB-regulated gene products, including inhibitor of apoptosis protein (IAP)-1, IAP-2, and X-linked IAP. Attenuation of NF-kappaB activity by pretreatment with PDTC, an NF-kappaB nuclear translocation inhibitor, significantly induced apoptosis in the presence of gossypol. Gossypol also suppressed NF-kappaB p65 mRNA accumulation, resulting in suppression of total NF-kappaB activity. This was associated with a downregulation of Sp1-binding activity, a transcription factor controlling p65 transcription. These results suggest that gossypol-induced apoptosis partially involves suppression of NF-kappaB activity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0304-3835
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
264
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
192-200
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18314260-Antineoplastic Agents, pubmed-meshheading:18314260-Apoptosis, pubmed-meshheading:18314260-Blotting, Western, pubmed-meshheading:18314260-Cell Proliferation, pubmed-meshheading:18314260-Dose-Response Relationship, Drug, pubmed-meshheading:18314260-Down-Regulation, pubmed-meshheading:18314260-Electrophoretic Mobility Shift Assay, pubmed-meshheading:18314260-Enzyme Activation, pubmed-meshheading:18314260-Flow Cytometry, pubmed-meshheading:18314260-Gene Expression, pubmed-meshheading:18314260-Gossypol, pubmed-meshheading:18314260-Humans, pubmed-meshheading:18314260-Leukemia, pubmed-meshheading:18314260-NF-kappa B, pubmed-meshheading:18314260-Protein Kinases, pubmed-meshheading:18314260-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:18314260-U937 Cells
pubmed:year
2008
pubmed:articleTitle
Gossypol suppresses NF-kappaB activity and NF-kappaB-related gene expression in human leukemia U937 cells.
pubmed:affiliation
Faculty of Applied Marine Science, Cheju National University, Jeju Special Self-Governing Province, 690-756, South Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't