Source:http://linkedlifedata.com/resource/pubmed/id/21484410
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
7
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| pubmed:dateCreated |
2011-5-20
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| pubmed:abstractText |
Despite all the progress in cancer treatment, glioblastoma, the most malignant tumor of the central nervous system, remains a terminal disease and new therapeutic approaches are urgently needed. A combination of chemotherapy with modifications that lower the apoptotic threshold of cancer cells could be effective. Cathepsin L inhibition was suggested as one of such modifications but the mechanism of cathepsin L anti-apoptotic activity is largely unknown. In the present study we show that, in U87 glioblastoma cells, cathepsin L is present in the nucleus and regulates the transcription of effector caspases 3 and 7. In cells with low cathepsin L expression, p53 and prohibitin--transcription factors that regulate caspase 7 expression--accumulate in the nuclei. The importance of p53 in this process is highlighted by the fact that in U87 cells with inhibited p53 transcriptional activity or in p53-negative cells U251, cathepsin L inhibition did not influence caspase 7 expression and had minimal effect on the level of apoptosis. Since p53 pathways are often mutated in glioblastoma, the findings of our study need to be considered before using cathepsin L inhibition for glioblastoma therapy and suggest that such adjuvant therapy may be effective only for a subpopulation of p53 wild type glioblastoma patients.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 7,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Cathepsin L,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53,
http://linkedlifedata.com/resource/pubmed/chemical/prohibitin
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jul
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| pubmed:issn |
1573-675X
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
16
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
671-82
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| pubmed:meshHeading |
pubmed-meshheading:21484410-Apoptosis,
pubmed-meshheading:21484410-Caspase 3,
pubmed-meshheading:21484410-Caspase 7,
pubmed-meshheading:21484410-Caspases,
pubmed-meshheading:21484410-Cathepsin L,
pubmed-meshheading:21484410-Cell Line, Tumor,
pubmed-meshheading:21484410-Cell Nucleus,
pubmed-meshheading:21484410-Down-Regulation,
pubmed-meshheading:21484410-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:21484410-Gene Silencing,
pubmed-meshheading:21484410-Glioblastoma,
pubmed-meshheading:21484410-Humans,
pubmed-meshheading:21484410-Lysosomes,
pubmed-meshheading:21484410-Mitochondrial Membranes,
pubmed-meshheading:21484410-Permeability,
pubmed-meshheading:21484410-Protein Transport,
pubmed-meshheading:21484410-RNA, Messenger,
pubmed-meshheading:21484410-Repressor Proteins,
pubmed-meshheading:21484410-Subcellular Fractions,
pubmed-meshheading:21484410-Transcription, Genetic,
pubmed-meshheading:21484410-Tumor Suppressor Protein p53,
pubmed-meshheading:21484410-Up-Regulation
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| pubmed:year |
2011
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| pubmed:articleTitle |
Inhibition of cathepsin L lowers the apoptotic threshold of glioblastoma cells by up-regulating p53 and transcription of caspases 3 and 7.
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| pubmed:affiliation |
Department of Genetic Toxicology and Cancer Biology, National Institue of Biology, Ljubljana, Slovenia. sasa.kenig@icgeb.org
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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