NDLI: Cellular uptake and subcellular distribution of ruthenium-based metallodrugs under clinical investigation versus cisplatin

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Cellular uptake and subcellular distribution of ruthenium-based metallodrugs under clinical investigation versus cisplatin

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Cellular uptake and subcellular distribution of ruthenium-based metallodrugs under clinical investigation versus cisplatin

Content Provider	Royal Society of Chemistry (RSC)
Author	Zava, Olivier Dyson, Paul J. Groessl, Michael
Copyright Year	2011
Abstract	The cellular uptake and subcellular distribution including adduct formation with genomic DNA and uptake into mitochondria of two ruthenium(III)-based drugs in clinical trials, KP1019 and NAMI-A, and cisplatin, was investigated in cisplatin sensitive and resistant A2780 human ovarian carcinoma cells. These data indicate that reduced metal uptake into mitochondria in combination with increased binding towards low molecular weight components involved in detoxification mechanisms is essential for cisplatin resistance. The ruthenium drugs show distinct differences with respect to cisplatin, especially in the cisplatin resistant cells; in comparison to the sensitive cells, KP1019 exhibits higher cytotoxicity and an only slightly changed metabolism of the drug, whereas NAMI-A treatment results in increased intracellular ruthenium levels and a higher number of ruthenium-DNA adducts. In addition, size exclusion-inductively coupled mass spectrometry indicates that adduct formation with high molecular weight components in the particulate and nuclear fractions is crucial for the therapeutic effect of KP1019 in both cisplatin resistant and sensitive cell lines.
Starting Page	591
Ending Page	599
Page Count	9
File Format	HTM / HTML PDF
ISSN	17565901
Volume Number	3
Issue Number	6
Journal	Metallomics
DOI	10.1039/c0mt00101e
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Mitochondrion Ruthenium Carcinoma DNA Cytotoxicity Metabolism Mass spectrometry Adduct Cisplatin
Content Type	Text
Resource Type	Article
Subject	Chemistry Medicine Metals and Alloys Biochemistry Biomaterials Biophysics

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