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Senolytic Effect of Cerium Oxide Nanoparticles (CeO2 NPs) by Attenuating p38/NF-кB, and p53/p21 Signaling Pathways

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Abstract

Oxidative stress induces cell senescence and aging. Cell senescence is an irreversible cell cycle arrest mechanism responsible for various pathological diseases and aging. Cerium oxide nanoparticles (CeO2 NPs) have been found to have anti-oxidant effects with a capacity to scavenge free radicals. With this background, we aimed to investigate the senolytic property of CeO2 NPs on mouse embryonic fibroblasts (NIH3T3). NIH3T3 cells were exposed to CeO2 NPs with or without hydrogen peroxide (H2O2). The senolytic effect of CeO2 NPs was evaluated by measuring reactive oxygen species (ROS) production, lipid peroxidation (LPO), β-galactosidase, cell cycle phase analysis, and expression of p21, p38, p53, and NF-кB genes. EC50 of CeO2 NPs significantly reduced the β-galactosidase activity in NIH3T3 cells without apparent cytotoxicity and generation of ROS. Also, it decreased LPO, and expression of IL-6. The number of cells increased significantly, indicating that CeO2 NPs can reverse cell senescence and cell cycle arrest in the S phase. Also, p21, p38, p53, and NF-кB gene expressions were significantly down-regulated. CeO2 NPs as a senolytic or inhibitor of senescence can attenuate the senescence-inducing signal transduction pathways, i.e., p38/ NF-кB and p53/p21. It reduced the production of ROS and LPO and the expression of IL-6.

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Acknowledgements

Research reported in this publication was supported by Elite Researcher Grant Committee under Award Number 977125 from the National Institutes for Medical Research Development (NIMAD), Tehran, Iran. Authors wish to thank Iran National Science Foundation (INSF) for general seat award support.

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  1. Hamed Haghi-Aminjan and Maryam Baeeri have equally contributed as first author.

Authors and Affiliations

  1. Pharmaceutical Sciences Research Center, Ardabil University of Medical Sciences, Ardabil, Iran

    Hamed Haghi-Aminjan

  2. Toxicology and Diseases Group, Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, 1417614411, Tehran, Iran

    Maryam Baeeri, Madiha Khalid, Mahban Rahimifard, Elaheh Mahdizadeh & Mohammad Abdollahi

  3. Department of Toxicology and Pharmacology, School of Pharmacy, Tehran University of Medical Sciences, 1417614411, Tehran, Iran

    Mohammad Reza Hooshangi Shayesteh & Mohammad Abdollahi

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  1. Hamed Haghi-Aminjan
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Haghi-Aminjan, H., Baeeri, M., Khalid, M. et al. Senolytic Effect of Cerium Oxide Nanoparticles (CeO2 NPs) by Attenuating p38/NF-кB, and p53/p21 Signaling Pathways. J Clust Sci 33, 2265–2275 (2022). https://doi.org/10.1007/s10876-021-02152-y

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