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

Martina Vermathen,Nico Ruprecht,Martin Nils Hungerbühler,Hendrik Von Tengg-Kobligk,Peter Vermathen

doi:10.3390/molecules26226766

Martina Vermathen, Nico Ruprecht + Show 3 more

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https://doi.org/10.3390/molecules26226766

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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.

Highlights

Cisplatin is an important drug that is used against various cancers, including advanced lung cancer
Several processes may contribute to cisPt resistance either alone, or concerted, including reduced cisPt uptake, increased cisPt excretion, intracellular deactivation of cisPt, or activation of DNA-damage repair and anti-apoptotic pathways [3,4]
Eight independent non-small cell lung cancer (NSCLC) cell lines with different and stable levels of cisPt resistance and derived from the same parental cisPt sensitive cell line allowed a systematic approach addressing the development of cisPt resistance

Summary

Introduction

Cisplatin (cisPt) is an important drug that is used against various cancers, including advanced lung cancer. Metabolites predominantly changed in cisPt resistant cells and their de-induced counterparts include glutathione and taurine. That accounts for 84% of all lung cancer diagnoses [2], cisPt resistance poses a major clinical problem [3]. The exact mechanisms accounting for metabolic adaptations in cisPt resistant cells are not well understood and to date the challenge of cisPt resistance has not been solved. The second group is characterized by the failure to induce apoptosis due to the formation of platinum-DNA adducts. Numerous approaches have been pursued to overcome cisPt resistance in cancer patients [5] None of these approaches could be implemented in the clinic so far [1]

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