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In Vitro Nephrotoxicity Studies of Established and Experimental Platinum-Based Compounds

Schoch, S.; Sen, V.; Brenner, W.; Hartwig, Andrea 1; Köberle, Beate 1
1 Institut für Toxikologie und Genetik (ITG), Karlsruher Institut für Technologie (KIT)


Cisplatin is one of the most commonly used drugs for the treatment of various solid cancers. However, its efficacy is restricted by severe side effects, especially dose-limiting nephrotoxicity. New platinum-based compounds are designed to overcome this limitation. Previous investigations showed that the platinum(IV)–nitroxyl complex PN149 is highly cytotoxic in various tumor cell lines. In the present study, investigations with PN149 were extended to normal human kidney tubule epithelia. Coincident with higher intracellular platinum accumulation, the cytotoxicity of PN149 in the proximal tubule epithelial cell line ciPTEC was more pronounced compared to the established platinum chemotherapeutics cisplatin, carboplatin and oxaliplatin. Quantitative gene expression profiling revealed the induction of ROS-inducible and anti-oxidative genes, suggesting an oxidative stress response by PN149. However, in contrast to cisplatin, no pro-inflammatory response was observed. Genes coding for distinct DNA damage response factors and genes related to apoptosis were up-regulated, indicating the activation of the DNA damage response system and induction of the apoptotic cascade by PN149. ... mehr

Verlagsausgabe §
DOI: 10.5445/IR/1000137471
Veröffentlicht am 01.10.2021
DOI: 10.3390/biomedicines9081033
Zitationen: 3
Web of Science
Zitationen: 2
Zitationen: 2
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Angewandte Biowissenschaften (IAB)
Publikationstyp Zeitschriftenaufsatz
Publikationsmonat/-jahr 08.2021
Sprache Englisch
Identifikator ISSN: 2227-9059
KITopen-ID: 1000137471
Erschienen in Biomedicines
Verlag MDPI
Band 9
Heft 8
Seiten 1033
Bemerkung zur Veröffentlichung Gefördert durch den KIT-Publikationsfonds
Nachgewiesen in Dimensions
Web of Science
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