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Comparative study of the mode of action of clinically approved platinum-based chemotherapeutics

Schoch, Sarah; Gajewski, Sabine; Rothfuß, Jana; Hartwig, Andrea; Köberle, Beate

Abstract:
Platinum drugs are among the most effective anticancer agents, but their mode of action is still not fully understood. We therefore carried out a systematic investigation on the cellular activities of cisplatin, carboplatin and oxaliplatin in A498 kidney cancer cells. Cytotoxicity was higher for cisplatin and oxaliplatin compared to carboplatin, with induction of apoptosis as the preferred mode of cell death. Gene expression profiling displayed modulation of genes related to DNA damage response/repair, cell cycle regulation and apoptosis which was more pronounced upon oxaliplatin treatment. Furthermore, repression of specific DNA repair genes was restricted to oxaliplatin. Transcriptional level observations were further analyzed on the functional level. Uptake studies revealed low intracellular platinum accumulation and DNA platination upon carboplatin treatment. Removal of overall DNA platination was comparable for the three drugs. However, no processing of oxaliplatin-induced interstrand crosslinks was observed. Cisplatin and carboplatin influenced cell cycle distribution comparably, while oxaliplatin had no effect. Altogether, we found a similar mode of action for cisplatin and carboplatin, while the activity of oxaliplatin appeared to differ. ... mehr

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Verlagsausgabe §
DOI: 10.5445/IR/1000125342
Veröffentlicht am 27.10.2020
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Angewandte Biowissenschaften (IAB)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2020
Sprache Englisch
Identifikator ISSN: 1422-0067, 1661-6596
KITopen-ID: 1000125342
Erschienen in International journal of molecular sciences
Band 21
Heft 18
Seiten 1-20
Schlagwörter cisplatin analogues; tumor cells; gene expression profiling; DNA damage response
Nachgewiesen in Scopus
Web of Science
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