1H HR-MAS NMR Based Metabolic Profiling of Lung Cancer Cells with Induced and De-Induced Cisplatin Resistance to Reveal Metabolic Resistance Adaptations

Molecules. 2021 Nov 9;26(22):6766. doi: 10.3390/molecules26226766.

Abstract

Cisplatin (cisPt) is an important drug that is used against various cancers, including advanced lung cancer. However, drug resistance is still a major ongoing problem and its investigation is of paramount interest. Here, a high-resolution magic angle spinning (HR-MAS) NMR study is presented deciphering the metabolic profile of non-small cell lung cancer (NSCLC) cells and metabolic adaptations at different levels of induced cisPt-resistance, as well as in their de-induced counterparts (cells cultivated in absence of cisPt). In total, fifty-three metabolites were identified and quantified in the 1H-HR-MAS NMR cell spectra. Metabolic adaptations to cisPt-resistance were detected, which correlated with the degree of resistance. Importantly, de-induced cell lines demonstrated similar metabolic adaptations as the corresponding cisPt-resistant cell lines. Metabolites predominantly changed in cisPt resistant cells and their de-induced counterparts include glutathione and taurine. Characteristic metabolic patterns for cisPt resistance may become relevant as biomarkers in cancer medicine.

Keywords: HR-MAS NMR; NSCLC; cisPt resistance; cisplatin; metabolomics; non-small cell lung cancer.

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cisplatin / pharmacology*
  • Drug Resistance, Neoplasm / drug effects*
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Metabolome*
  • Nuclear Magnetic Resonance, Biomolecular*

Substances

  • Cisplatin