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Thiazolides promote apoptosis in colorectal tumor cells via MAP kinase-induced Bim and Puma activation

Thiazolides promote apoptosis in colorectal tumor cells via MAP kinase-induced Bim and Puma activation

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BROCKMANN, Anette, Andrej BLUWSTEIN, Annika KÖGEL, Sarah MAY, Andreas MARX, Mario P. TSCHAN, Thomas BRUNNER, 2015. Thiazolides promote apoptosis in colorectal tumor cells via MAP kinase-induced Bim and Puma activation. In: Cell Death & Disease. 6, e1778. eISSN 2041-4889

@article{Brockmann2015Thiaz-31127, title={Thiazolides promote apoptosis in colorectal tumor cells via MAP kinase-induced Bim and Puma activation}, year={2015}, doi={10.1038/cddis.2015.137}, volume={6}, journal={Cell Death & Disease}, author={Brockmann, Anette and Bluwstein, Andrej and Kögel, Annika and May, Sarah and Marx, Andreas and Tschan, Mario P. and Brunner, Thomas}, note={Article Number: e1778} }

<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/31127"> <dc:language>eng</dc:language> <dc:contributor>Tschan, Mario P.</dc:contributor> <dc:creator>Marx, Andreas</dc:creator> <dc:contributor>Bluwstein, Andrej</dc:contributor> <dc:creator>Tschan, Mario P.</dc:creator> <dc:contributor>Kögel, Annika</dc:contributor> <dc:contributor>May, Sarah</dc:contributor> <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/31127"/> <dcterms:rights rdf:resource="http://nbn-resolving.de/urn:nbn:de:bsz:352-20150305140228786-3747162-5"/> <dc:creator>Brockmann, Anette</dc:creator> <dc:creator>Bluwstein, Andrej</dc:creator> <dc:creator>Brunner, Thomas</dc:creator> <dcterms:abstract xml:lang="eng">While many anticancer therapies aim to target the death of tumor cells, sophisticated resistance mechanisms in the tumor cells prevent cell death induction. In particular enzymes of the glutathion-S-transferase (GST) family represent a well-known detoxification mechanism, which limit the effect of chemotherapeutic drugs in tumor cells. Specifically, GST of the class P1 (GSTP1-1) is overexpressed in colorectal tumor cells and renders them resistant to various drugs. Thus, GSTP1-1 has become an important therapeutic target. We have recently shown that thiazolides, a novel class of anti-infectious drugs, induce apoptosis in colorectal tumor cells in a GSTP1-1-dependent manner, thereby bypassing this GSTP1-1-mediated drug resistance. In this study we investigated in detail the underlying mechanism of thiazolide-induced apoptosis induction in colorectal tumor cells. Thiazolides induce the activation of p38 and Jun kinase, which is required for thiazolide-induced cell death. Activation of these MAP kinases results in increased expression of the pro-apoptotic Bcl-2 homologs Bim and Puma, which inducibly bind and sequester Mcl-1 and Bcl-xL leading to the induction of the mitochondrial apoptosis pathway. Of interest, while an increase in intracellular glutathione levels resulted in increased resistance to cisplatin, it sensitized colorectal tumor cells to thiazolide-induced apoptosis by promoting increased Jun kinase activation and Bim induction. Thus, thiazolides may represent an interesting novel class of anti-tumor agents by specifically targeting tumor resistance mechanisms, such as GSTP1-1.</dcterms:abstract> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2015-06-10T08:56:09Z</dcterms:available> <dc:creator>May, Sarah</dc:creator> <dcterms:title>Thiazolides promote apoptosis in colorectal tumor cells via MAP kinase-induced Bim and Puma activation</dcterms:title> <dc:contributor>Marx, Andreas</dc:contributor> <dc:contributor>Brockmann, Anette</dc:contributor> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2015-06-10T08:56:09Z</dc:date> <dcterms:issued>2015</dcterms:issued> <dc:creator>Kögel, Annika</dc:creator> <dc:contributor>Brunner, Thomas</dc:contributor> </rdf:Description> </rdf:RDF>

Dateiabrufe seit 10.06.2015 (Informationen über die Zugriffsstatistik)

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