1H HR-MAS NMR Based Metabolic Profiling of Cells in Response to Treatment with a Hexacationic Ruthenium Metallaprism as Potential Anticancer Drug

PLoS One. 2015 May 29;10(5):e0128478. doi: 10.1371/journal.pone.0128478. eCollection 2015.

Abstract

(1)H 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Drug Screening Assays, Antitumor
  • HEK293 Cells
  • Humans
  • Magnetic Resonance Spectroscopy
  • Metabolome / drug effects*
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology*
  • Ruthenium / chemistry
  • Ruthenium / pharmacology*

Substances

  • Antineoplastic Agents
  • Organometallic Compounds
  • Ruthenium

Grants and funding

Financial supports from the Department of Chemistry & Biochemistry at the University of Bern (http://www.dcb.unibe.ch/content/index_ger.html) (JF) and from the Swiss National Science Foundation SNF (http://www.snf.ch/en/Pages/default.aspx) grants # 206021-128736 (MV, PV), # 200021_149438 (MV, JF), and # 320030-138150 (PV) are greatly acknowledged. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.