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dc.contributor.author
Khageh Hosseini, Sabrina
dc.contributor.author
Kolterer, Stefanie
dc.contributor.author
Steiner, Marlene
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von Manstein, Viktoria
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Gerlach, Katharina
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Trojan, Jörg
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Waidmann, Oliver
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Zeuzem, Stefan
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Schulze, Jörg O.
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Hahn, Steffen
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Steinhilber, Dieter
dc.contributor.author
Gatterdam, Volker
dc.contributor.author
Tampé, Robert
dc.contributor.author
Biondi, Ricardo Miguel
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Proschak, Ewgenij
dc.contributor.author
Zörnig, Martin
dc.date.available
2018-07-06T15:52:37Z
dc.date.issued
2017-12
dc.identifier.citation
Khageh Hosseini, Sabrina; Kolterer, Stefanie; Steiner, Marlene; von Manstein, Viktoria; Gerlach, Katharina; et al.; Camptothecin and its analog SN-38, the active metabolite of irinotecan, inhibit binding of the transcriptional regulator and oncoprotein FUBP1 to its DNA target sequence FUSE; Pergamon-Elsevier Science Ltd; Biochemical Pharmacology; 146; 12-2017; 53-62
dc.identifier.issn
0006-2952
dc.identifier.uri
http://hdl.handle.net/11336/51497
dc.description.abstract
The transcriptional regulator FUSE Binding Protein 1 (FUBP1) is overexpressed in more than 80% of all human hepatocellular carcinomas (HCCs) and other solid tumor entities including prostate and colorectal carcinoma. FUBP1 expression is required for HCC tumor cell expansion, and it functions as an important pro-proliferative and anti-apoptotic oncoprotein that binds to the single-stranded DNA sequence FUSE to regulate the transcription of a variety of target genes. In this study, we screened an FDA-approved drug library and discovered that the Topoisomerase I (TOP1) inhibitor camptothecin (CPT) and its derivative 7-ethyl-10-hydroxycamptothecin (SN-38), the active irinotecan metabolite that is used in the clinics in combination with other chemotherapeutics to treat carcinoma, inhibit FUBP1 activity. Both molecules prevent in vitro the binding of FUBP1 to its single-stranded target DNA FUSE, and they induce deregulation of FUBP1 target genes in HCC cells. Our results suggest the interference with the FUBP1/FUSE interaction as a further molecular mechanism that, in addition to the inactivation of TOP1, may contribute to the therapeutic potential of CPT/SN-38. Targeting of FUBP1 in HCC therapy with SN-38/irinotecan could be a particularly interesting option because of the high FUBP1 levels in HCC cells and their dependency on FUBP1 expression.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Pergamon-Elsevier Science Ltd
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Alphascreen
dc.subject
Camptothecin
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Fubp1
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Hcc
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Sn-38
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Otras Ciencias Biológicas
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dc.subject.classification
Ciencias Biológicas
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dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
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dc.title
Camptothecin and its analog SN-38, the active metabolite of irinotecan, inhibit binding of the transcriptional regulator and oncoprotein FUBP1 to its DNA target sequence FUSE
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-06-19T15:59:27Z
dc.journal.volume
146
dc.journal.pagination
53-62
dc.journal.pais
Estados Unidos
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dc.journal.ciudad
Nueva York
dc.description.fil
Fil: Khageh Hosseini, Sabrina. Georg Speyer Haus; Alemania
dc.description.fil
Fil: Kolterer, Stefanie. Georg Speyer Haus; Alemania
dc.description.fil
Fil: Steiner, Marlene. Georg Speyer Haus; Alemania
dc.description.fil
Fil: von Manstein, Viktoria. Georg Speyer Haus; Alemania
dc.description.fil
Fil: Gerlach, Katharina. Georg Speyer Haus; Alemania
dc.description.fil
Fil: Trojan, Jörg. University Hospital Frankfurt; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
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Fil: Waidmann, Oliver. University Hospital Frankfurt; Alemania
dc.description.fil
Fil: Zeuzem, Stefan. University Hospital Frankfurt; Alemania
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Fil: Schulze, Jörg O.. University Hospital Frankfurt; Alemania
dc.description.fil
Fil: Hahn, Steffen. Goethe Universitat Frankfurt; Alemania
dc.description.fil
Fil: Steinhilber, Dieter. Goethe Universitat Frankfurt; Alemania
dc.description.fil
Fil: Gatterdam, Volker. Goethe Universitat Frankfurt; Alemania
dc.description.fil
Fil: Tampé, Robert. Goethe Universitat Frankfurt; Alemania
dc.description.fil
Fil: Biondi, Ricardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina. University Hospital Frankfurt; Alemania
dc.description.fil
Fil: Proschak, Ewgenij. Goethe Universitat Frankfurt; Alemania. German Cancer Consortium; Alemania
dc.description.fil
Fil: Zörnig, Martin. German Cancer Consortium; Alemania. Georg Speyer Haus; Alemania
dc.journal.title
Biochemical Pharmacology
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.bcp.2017.10.003
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0006295217306330
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