Linked Life Data

20515942

Source:http://linkedlifedata.com/resource/pubmed/id/20515942

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2010-6-11
pubmed:abstractText
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces cell death in various types of cancer cells but has little or no effect on normal cells. Human hepatoma cells are resistant to TRAIL-induced apoptosis. Although butein is known to mediate anticancer, anti-inflammatory, and antioxidant activities, little is known about the mechanism of butein in terms of TRAIL-induced apoptosis of human hepatoma cells. In this study, we determined that butein enhances TRAIL-induced apoptosis in hepatoma cells through upregulation of DR5. Luciferase analysis showed that a 5'-flanking region containing four Sp1-binding sites within the DR5 promoter was enhanced by butein (-305/-300). Electrophoretic mobility shift assays and chromatin immunoprecipitation studies were used to analyze the elevation of Sp1 binding to DR5 promoter sites by butein. Point mutations of the Sp1-binding site also attenuated promoter activity. Furthermore, pretreatment of the blocking chimeric antibody and small interfering RNA for DR5 significantly suppressed TRAIL-mediated apoptosis by butein in Hep3B cells. Butein also stimulated extracellular signal-regulated kinase (ERK) activation, and the ERK inhibitor PD98059 blocked butein-induced DR5 expression and suppressed binding of Sp1 to the DR5 promoter. Additionally, generation of reactive oxygen species had no effect on cell viability, although pretreatment with N-acetyl-l-cysteine or glutathione inhibited combined treatment-induced reactive oxygen species. Indeed, butein repressed the TRAIL-mediated activation of NF-kappaB and decreased its transcriptional activity. Our results suggest that butein could sensitize certain human hepatoma cells to TRAIL-induced apoptosis through stimulating its death signaling and by repressing the survival function in these cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1538-8514
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1583-95
pubmed:meshHeading
pubmed-meshheading:20515942-Apoptosis, pubmed-meshheading:20515942-Carcinoma, Hepatocellular, pubmed-meshheading:20515942-Caspases, pubmed-meshheading:20515942-Cell Line, Tumor, pubmed-meshheading:20515942-Chalcones, pubmed-meshheading:20515942-Drug Screening Assays, Antitumor, pubmed-meshheading:20515942-Drug Synergism, pubmed-meshheading:20515942-Enzyme Activation, pubmed-meshheading:20515942-Extracellular Signal-Regulated MAP Kinases, pubmed-meshheading:20515942-Gene Expression Regulation, Neoplastic, pubmed-meshheading:20515942-Humans, pubmed-meshheading:20515942-Liver Neoplasms, pubmed-meshheading:20515942-NF-kappa B, pubmed-meshheading:20515942-Organ Specificity, pubmed-meshheading:20515942-Promoter Regions, Genetic, pubmed-meshheading:20515942-Receptors, TNF-Related Apoptosis-Inducing Ligand, pubmed-meshheading:20515942-Signal Transduction, pubmed-meshheading:20515942-Sp1 Transcription Factor, pubmed-meshheading:20515942-TNF-Related Apoptosis-Inducing Ligand, pubmed-meshheading:20515942-Transcription, Genetic, pubmed-meshheading:20515942-Up-Regulation
pubmed:year
2010
pubmed:articleTitle
Butein sensitizes human hepatoma cells to TRAIL-induced apoptosis via extracellular signal-regulated kinase/Sp1-dependent DR5 upregulation and NF-kappaB inactivation.
pubmed:affiliation
Laboratory of Immunobiology, Department of Marine Life Science, Jeju National University, Jeju, Republic of Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't