Chemosensitization effect of cerium oxide nanosheets by suppressing drug detoxification and efflux.

Author(s) Wu, G.; Zhang, Z.; Chen, X.; Yu, Q.; Ma, X.; Liu, L.
Journal Ecotoxicol Environ Saf
Date Published 2019 Jan 15
Abstract

Cerium oxide (CeO) nanomaterials (NMs) have wide applications in biomedicine and are also detected with increasing bioaccumulation in various biological and environmental media. Thus, a system was developed to evaluate the chemosensitization effect of CeO NMs. Herein, we discovered that low doses of CeO NMs could trigger reactive oxygen species (ROS) production and decrease mitochondrial membrane potential (MMP) without causing severe toxicity to cancer cells, while pretreatment of the cells with CeO NMs enhanced the toxicity of the chemotherapeutic agent doxorubicin (DOX). The reduced efflux of DOX was mainly attributed to adenosine triphosphate (ATP) depletion, followed by attenuation of exocytosis and enhancement of DOX retention. Further investigations revealed that CeO NM-induced ROS production caused depletion of intracellular glutathione (GSH) and consequent impairment of DOX detoxification. Moreover, CeO NMs were found to enhance the chemosensitization of cancer cells rather than normal cells. Thus, this study uncovered the underlying application potential of CeO NMs in cancer therapy by enhancing the efficacy of chemotherapeutic agent, which is associated with disruption of mitochondrial function and impairment of drug detoxification.

DOI 10.1016/j.ecoenv.2018.10.013
Keywords A549 Cells; Adenosine Triphosphate; Animals; Apoptosis; Cell Line, Tumor; Cell Survival; Cerium; Dose-Response Relationship, Drug; Doxorubicin; Glutathione; Humans; Inactivation, Metabolic; Membrane Potential, Mitochondrial; Nanostructures; Rats; Reactive Oxygen Species
ISSN 1090-2414
Citation Wu G, Zhang Z, Chen X, Yu Q, Ma X, Liu L. Chemosensitization effect of cerium oxide nanosheets by suppressing drug detoxification and efflux. Ecotoxicol Environ Saf. 2019;167:301-308.

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