Dose responsive effects of cisplatin in L02 cells using NMR-based metabolomics

Cisplatin is an effective chemotherapeutic agent for the treatment of various cancers, such as bladder cancer, epithelial ovarian cancer, cervical cancer, and so on. However, cisplatin can cause various side effects. In this study, the dose-responsive effects of cisplatin were investigated in an in vitro model of human liver cells (L02) using NMR-based metabolomics. The inverted U-shaped curve of cell proliferation confirmed the hormetic effects of cisplatin (from 1 nM to 1 mM) in L02 cells. However, the metabolite changes revealed both U-shaped (ethanol, lactate, aspartate, choline, etc.) and inverted U-shaped (glutamate, glutamine, 4-aminobutyrate, myo-inositol, etc.) curves induced by three typical concentrations of cisplatin which covered the inverted U-shaped curve as indicated by the cell proliferation assay. These findings suggested that a macroscopic hormesis phenomenon on the cell proliferation could be reflected by both stimulated and inhibited metabolites and corresponding metabolic pathways to cisplatin treatments. Therefore, a global analysis using metabolomics may give a broader view into the dose-response relationship than using a single endpoint at molecular levels.