NDLI: In vitro characterization of a novel C,N-cyclometalated benzimidazole Ru(ii) arene complex: stability, intracellular distribution and binding, effects on organic osmolyte homeostasis and induction of apoptosis

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Metallomics Vol - 7 Issue - 4

Metallomics Vol - 7 Issue - 3

Metallomics Vol - 7 Issue - 2

In vitro characterization of a novel C,N-cyclometalated benzimidazole Ru(ii) arene complex: stability, intracellular distribution and binding, effects on organic osmolyte homeostasis and induction of apoptosis

Content Provider	Royal Society of Chemistry (RSC)
Author	Henarejos, Sergio Alejo Perez Yellol, Gorakh S. Gammelgaard, Bente Dam, Celina Støving Tsolakou, Theodosia Segato, Christian Alexander Stürup, Stefan Lambert, Ian Henry Ruiz, José
Copyright Year	2015
Abstract	In the present work a novel C,N-cyclometalated benzimidazole Ru(II) arene complex (GY34) was characterized by applying an alternative, diverse approach considering both chemical and biological aspects. RP-HPLC-ICP-MS and RP-HPLC-ESI-MS analysis proved that GY34 in both RPMI-1640 cell medium and ammonium acetate buffer was transformed into several subspecies and the importance of evaluating and controlling analyte stability throughout experiments was demonstrated. Applying a novel cell fractionation protocol GY34 was found to target cell nuclei and mitochondria in Ehrlich Lettré Ascites (ELA) cells, with the intracellular distribution depending on GY34 concentration in the cell medium during incubation. In ELA cells 96 ± 0.2% of cytosolic GY34 was bound to high-molecular species. Furthermore, using the tracer technique GY34 was found to reduce uptake and increase release of the organic osmolyte taurine in ELA cells, with innate resistance to Cisplatin and in A2780 human ovarian cancer cells, with acquired resistance to Cisplatin. Importantly, FACS analysis revealed that GY34 induced apoptosis in ELA cells. The present data suggest the potential of GY34 in overcoming Cisplatin resistance. The methodology applied can be used as a general protocol and an additional tool in the initial evaluation of novel metal-based drugs.
Starting Page	885
Ending Page	895
Page Count	11
File Format	HTM / HTML PDF
ISSN	17565901
Volume Number	7
Issue Number	5
Journal	Metallomics
DOI	10.1039/c5mt00056d
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Analyte Taurine Flow cytometry Ammonium Cell nucleus Cell fractionation Ehrlich Subspecies Cisplatin Ovarian cancer Mitochondrion Benzimidazole Ascites Osmolyte Apoptosis
Content Type	Text
Resource Type	Article
Subject	Chemistry Medicine Metals and Alloys Biochemistry Biomaterials Biophysics

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