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Liu S.,The 2nd Peoples Hospital of Huaian | Wang W.,The 2nd Peoples Hospital of Huaian | Zhou X.,The 2nd Peoples Hospital of Huaian | Ding Z.,The 2nd Peoples Hospital of Huaian | Gu R.,The 2nd Peoples Hospital of Huaian
Environmental Toxicology and Pharmacology | Year: 2015

Cisplatin is a chemotherapeutic agent for the treatment of various cancers. In this study, cisplatin-induced effects were characterized in vitro model of human liver cells (L02) using 2-DE-based proteomics. Results indicated that different cisplatin treatments primarily induced disturbances in protein synthesis and oxidative stress via differential mechanisms. Since the experimental concentrations of cisplatin described a hormesis effect in cell proliferation of L02 cells, it was expected to reveal the hormesis effects using proteomic markers. However, only confilin-1 was commonly up-regulated in three concentrations of cisplatin treatments showing a hormesis effects with a U-shape regulation. These results were highly consistent with many other toxico-proteomic studies, indicating that the toxico-proteomic responses based on dose-dependent protein responses were incongruent with the theoretically linear or hormetic concentration-effect relationship. Our findings suggested that a macroscopic hormesis phenomenon on the cell proliferation could not be reflected by proteomic responses induced by cisplatin treatments. © 2014 Elsevier B.V. Source


Liu S.,The 2nd Peoples Hospital of Huaian | Wang W.,The 2nd Peoples Hospital of Huaian | Zhou X.,The 2nd Peoples Hospital of Huaian | Gu R.,The 2nd Peoples Hospital of Huaian | Ding Z.,The 2nd Peoples Hospital of Huaian
Environmental Toxicology and Pharmacology | Year: 2014

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. © 2013 Elsevier B.V. Source

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