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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2009-4-10
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pubmed:abstractText |
Recent studies establish a critical role of selenium in cancer prevention in vitro and in vivo. Selenium may sensitize TRAIL-mediated apoptosis in human renal cancer cells and increase therapeutic efficacy. In this study, we demonstrate that concomitant administration of TRAIL and Se-methylselenocysteine (Se-MSC) produces synergistic effects on the induction of apoptosis in Caki cells. Se-MSC rapidly and specifically down-regulates expression of the Bcl-2 at transcriptional level. The forced expression of Bcl-2 attenuated Se-MSC plus TRAIL-mediated apoptosis, suggesting that the lessened Bcl-2 expression caused by Se-MSC treatment is critical to the increased sensitivity to TRAIL in renal cancer cells. In addition, we demonstrate that the synergistic effects of Se-MSC and TRAIL result from the activation of the caspase-dependent pathways. Co-administration of HA14-1, a small molecule Bcl-2 inhibitor and TRAIL increased apoptosis in Caki cells. Taken together, Se-MSC-mediated down-regulation of Bcl-2 is able to sensitize Caki cells for TRAIL-induced apoptosis. Thus, selenium-based dietary compounds may help to overcome resistance to TRAIL-mediated apoptosis in renal cancer cells.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1019-6439
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
34
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1455-60
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pubmed:meshHeading |
pubmed-meshheading:19360359-Antineoplastic Combined Chemotherapy Protocols,
pubmed-meshheading:19360359-Apoptosis,
pubmed-meshheading:19360359-Carcinoma,
pubmed-meshheading:19360359-Caspases,
pubmed-meshheading:19360359-Cysteine,
pubmed-meshheading:19360359-Down-Regulation,
pubmed-meshheading:19360359-Drug Evaluation, Preclinical,
pubmed-meshheading:19360359-Drug Synergism,
pubmed-meshheading:19360359-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:19360359-Genes, bcl-2,
pubmed-meshheading:19360359-Humans,
pubmed-meshheading:19360359-Kidney Neoplasms,
pubmed-meshheading:19360359-Organoselenium Compounds,
pubmed-meshheading:19360359-Peptide Fragments,
pubmed-meshheading:19360359-Proto-Oncogene Proteins,
pubmed-meshheading:19360359-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:19360359-TNF-Related Apoptosis-Inducing Ligand,
pubmed-meshheading:19360359-Tumor Cells, Cultured
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pubmed:year |
2009
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pubmed:articleTitle |
Se-methylselenocysteine sensitized TRAIL-mediated apoptosis via down-regulation of Bcl-2 expression.
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pubmed:affiliation |
Department of Immunology and Chronic Disease Research Center and Institute for Medical Science, School of Medicine, Keimyung University, Jung-Gu, Taegu 700-712, Korea.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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