Abstract
1H high resolution magic angle spinning (HR-MAS) NMR spectroscopy was applied in combination with multivariate statistical analyses to study the metabolic response of whole cells to the treatment with a hexacationic ruthenium metallaprism [1]6+ as potential anticancer drug. Human ovarian cancer cells (A2780), the corresponding cisplatin resistant cells (A2780cisR), and human embryonic kidney cells (HEK-293) were each incubated for 24 h and 72 h with [1]6+ and compared to untreated cells. Different responses were obtained depending on the cell type and incubation time. Most pronounced changes were found for lipids, choline containing compounds, glutamate and glutathione, nucleotide sugars, lactate, and some amino acids. Possible contributions of these metabolites to physiologic processes are discussed. The time-dependent metabolic response patterns suggest that A2780 cells on one hand and HEK-293 cells and A2780cisR cells on the other hand may follow different cell death pathways and exist in different temporal stages thereof.
Highlights
Following the success of platinum-based anticancer drugs, with cisplatin [1] being the most widely used compound in this field [2], much attention has been given to ruthenium complexes as alternative agents to overcome some of the drawbacks associated with platinum-based treatment such as general toxicity, drug resistance or low selectivity [3,4]
We report on the hexacationic ruthenium metallaprism [p-cymene)6Ru6(tpt)2(dhnq)3] (CF3SO3)6, [1]6+, shown in Fig 1, and its effect on the metabolic profile of cancerous and noncancerous cultured cells
1H high resolution magic angle spinning (HR-MAS) NMR spectra of cells In Fig 2, a representative 1H HR-MAS NMR spectrum with some of the resonances assigned to specific cell metabolites is shown for a suspension of A2780 human ovarian carcinoma cells in phosphate buffered saline (PBS)
Summary
Following the success of platinum-based anticancer drugs, with cisplatin [1] being the most widely used compound in this field [2], much attention has been given to ruthenium complexes as alternative agents to overcome some of the drawbacks associated with platinum-based treatment such as general toxicity, drug resistance or low selectivity [3,4]. Different types of ruthenium based complexes have been developed as promising anticancer drug candidates. Two Ru (III) complexes, KP1019 (NKP1339) [5] and NAMI-A [6,7], both bearing imidazole and chloride ligands, have reached phase II clinical trials [8]. KP1019 is more effective against primary tumors, while NAMI-A is more effective against metastasis, and both exhibit an increased selectivity leading to fewer side effects [9]. PLOS ONE | DOI:10.1371/journal.pone.0128478 May 29, 2015
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
