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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-12-24
pubmed:abstractText
Berberine (BBR) is an isoquinoline alkaloid which has a wide spectrum of clinical applications including anti-tumor, anti-microbial and anti-inflammatory activities. In this study, we showed that co-treatment with subtoxic doses of BBR and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induced apoptosis in human renal cancer cells, Caki cells, but not in normal tubular kidney cells. Treatment of Caki cells with BBR resulted in downregulation of c-FLIP and Mcl-1 proteins in a dose-dependent manner. The BBR-induced downregulation of c-FLIP and Mcl-1 proteins were involved in proteasome dependent pathways, which was confirmed by the result that pre-treatment with the proteasome inhibitor MG132 inhibited berberine-induced downregulation of the c-FLIP and Mcl-1 proteins. Pretreatment with N-acetyl-L-cysteine (NAC) significantly inhibited the cell death induced by the combined treatment with BBR and TRAIL as well as recovered the expression levels of c-FLIP and Mcl-1 downregulated by treatment with BBR. These results suggested that BBR-stimulated TRAIL-induced apoptosis is dependent on the generation of reactive oxygen species through the downregulation of c-FLIP and Mcl-1 proteins. In conclusion, this study demonstrates that BBR enhances TRAIL-induced apoptosis in human renal cancer cells by ROS-mediated c-FLIP and Mcl-1 down-regulation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1791-2423
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
485-92
pubmed:meshHeading
pubmed-meshheading:21170508-Apoptosis, pubmed-meshheading:21170508-Berberine, pubmed-meshheading:21170508-Blotting, Western, pubmed-meshheading:21170508-CASP8 and FADD-Like Apoptosis Regulating Protein, pubmed-meshheading:21170508-Cell Line, Tumor, pubmed-meshheading:21170508-Cell Proliferation, pubmed-meshheading:21170508-Down-Regulation, pubmed-meshheading:21170508-Flow Cytometry, pubmed-meshheading:21170508-Humans, pubmed-meshheading:21170508-Kidney Neoplasms, pubmed-meshheading:21170508-Proteasome Endopeptidase Complex, pubmed-meshheading:21170508-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:21170508-RNA, Messenger, pubmed-meshheading:21170508-Reactive Oxygen Species, pubmed-meshheading:21170508-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:21170508-TNF-Related Apoptosis-Inducing Ligand
pubmed:year
2011
pubmed:articleTitle
Berberine sensitizes TRAIL-induced apoptosis through proteasome-mediated downregulation of c-FLIP and Mcl-1 proteins.
pubmed:affiliation
Department of Anatomy, College of Medicine, Yeungnam University, 317-1 Daemyung-Dong Nam-Gu, Daegu 705-717, Republic of Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't