Preclinical studies on metal based anticancer drugs as enabled by integrated metallomics and metabolomics

Luis Galvez, Mate Rusz, Michaela Schwaiger-Haber, Yasin El Abiead, Gerrit Hermann, Ute Jungwirth, Walter Berger, Bernhard K. Keppler, Michael A. Jakupec, Gunda Koellensperger

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Resistance development is a major obstacle for platinum-based chemotherapy, with the anticancer drug oxaliplatin being no exception. Acquired resistance is often associated with altered drug accumulation. In this work we introduce a novel -omics workflow enabling the parallel study of platinum drug uptake and its distribution between nucleus/protein and small molecule fraction along with metabolic changes after different treatment time points. This integrated metallomics/metabolomics approach is facilitated by a tailored sample preparation workflow suitable for preclinical studies on adherent cancer cell models. Inductively coupled plasma mass spectrometry monitors the platinum drug, while the metabolomics tool-set is provided by hydrophilic interaction liquid chromatography combined with high-resolution Orbitrap mass spectrometry. The implemented method covers biochemical key pathways of cancer cell metabolism as shown by a panel of >130 metabolite standards. Furthermore, the addition of yeast-based 13C-enriched internal standards upon extraction enabled a novel targeted/untargeted analysis strategy. In this study we used our method to compare an oxaliplatin sensitive human colon cancer cell line (HCT116) and its corresponding resistant model. In the acquired oxaliplatin resistant cells distinct differences in oxaliplatin accumulation correlated with differences in metabolomic rearrangements. Using this multi-omics approach for platinum-treated samples facilitates the generation of novel hypotheses regarding the susceptibility and resistance towards oxaliplatin.

Original languageEnglish
Pages (from-to)1716-1728
Number of pages13
JournalMetallomics
Volume11
Issue number10
Early online date29 Aug 2019
DOIs
Publication statusPublished - 1 Oct 2019

ASJC Scopus subject areas

  • Chemistry (miscellaneous)
  • Biophysics
  • Biomaterials
  • Biochemistry
  • Metals and Alloys

Cite this

Galvez, L., Rusz, M., Schwaiger-Haber, M., El Abiead, Y., Hermann, G., Jungwirth, U., Berger, W., Keppler, B. K., Jakupec, M. A., & Koellensperger, G. (2019). Preclinical studies on metal based anticancer drugs as enabled by integrated metallomics and metabolomics. Metallomics, 11(10), 1716-1728. https://doi.org/10.1039/c9mt00141g