Cytotoxicity Produced by Silicate Nanoplatelets: Study of Cell Death Mechanisms
1
Department of Animal Science, National Chung Hsing University, Taichung 40227, Taiwan
2
Chinese Medicinal Research and Development Center, China Medical University Hospital, Taichung 40447, Taiwan
3
Center for Molecular Medicine, China Medical University Hospital, Taichung 40447, Taiwan
4
Department of Biological Science and Technology, China Medical University, Taichung 40402, Taiwan
5
Department of Materials Science and Engineering, National Chung Hsing University, Taichung 40227, Taiwan
6
The iEGG and Animal Biotechnology Center, National Chung Hsing University, Taichung 40227, Taiwan
7
Innovation and Development Center of Sustainable Agriculture (IDCSA), National Chung Hsing University, Taichung 40227, Taiwan
8
Research Center for Sustainable Energy and Nanotechnology, National Chung Hsing University, Taichung 40227, Taiwan
*
Author to whom correspondence should be addressed.
†
These two authors contribute equally to this work.
Toxins 2020, 12(10), 623; https://doi.org/10.3390/toxins12100623
Received: 26 August 2020
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Revised: 18 September 2020
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Accepted: 29 September 2020
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Published: 29 September 2020
(This article belongs to the Special Issue Evaluation of Cytotoxicity and Cytoprotection Effects of Natural Toxins)
Nano-silicate platelets (NSP), an exfoliated product from natural clays, have been validated for biosafety and as an effective supplement to alleviate mycotoxicosis. Since NSP induced noticeable cell death, we therefore investigated further the mechanism of cytotoxicity caused by NSP. Exposure to NSP impaired membrane integrity and caused cell death in a dose-dependent manner. Reactive oxygen species (ROS) generation other than of NADH oxidase origin, and subcellular interactions by internalized NSP also contributed to NSP-induced cell death. NSP persistently provoked receptor-interacting protein 1 Ser/Thr (RIP1) kinase and caspase 6 and 3/7 activation without altering caspase 8 activity and induced evident chromatolysis of necrosis in the later stage. These events proceeded along with increased ER stress and mitochondrial permeability, to final Cyt-C (Cytochrome C) release and AIF (apoptosis inducing factor) translocation, a hallmark of cell necroptosis. Fluorescent probing further manifested NSP traffic, mostly adherence on the cell surfaces, or via internalization, being compartmentalized in the nuclei, cytosols, and mitochondria. Pharmacological approaches with specific inhibitors suggested that endocytosis and particularly RIP1 kinase provocation mediate NSP-induced cell death independent of caspase activation. In conclusion, the necroptotic process contributes to most of the cell death induced by NSP due to membrane interactions/impaired integrity, ROS generation, and subcellular interactions by internalized NSP.
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Keywords:
nano-silicate platelets; necroptosis; reactive oxygen species; endocytosis; membrane integrity
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MDPI and ACS Style
Huang, J.-T.; Chang, L.-C.; Cheng, C.-S.; Lin, J.-J.; Huang, S.-Y.; Chen, S.-E. Cytotoxicity Produced by Silicate Nanoplatelets: Study of Cell Death Mechanisms. Toxins 2020, 12, 623. https://doi.org/10.3390/toxins12100623
AMA Style
Huang J-T, Chang L-C, Cheng C-S, Lin J-J, Huang S-Y, Chen S-E. Cytotoxicity Produced by Silicate Nanoplatelets: Study of Cell Death Mechanisms. Toxins. 2020; 12(10):623. https://doi.org/10.3390/toxins12100623
Chicago/Turabian StyleHuang, Jie-Ting, Ling-Chu Chang, Chung-Ssu Cheng, Jiang-Jen Lin, San-Yuan Huang, and Shuen-Ei Chen. 2020. "Cytotoxicity Produced by Silicate Nanoplatelets: Study of Cell Death Mechanisms" Toxins 12, no. 10: 623. https://doi.org/10.3390/toxins12100623
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