PUBLICATION
ZnO Nanoparticles Induced Caspase-Dependent Apoptosis in Gingival Squamous Cell Carcinoma through Mitochondrial Dysfunction and p70S6K Signaling Pathway
- Authors
- L, S.W., Lee, C.H., Lin, M.S., Chi, C.W., Chen, Y.J., Wang, G.S., Liao, K.W., Chiu, L.P., Wu, S.H., Huang, D.M., Chen, L., Shen, Y.S.
- ID
- ZDB-PUB-200301-2
- Date
- 2020
- Source
- International Journal of Molecular Sciences 21(5): (Journal)
- Registered Authors
- Keywords
- gingival cancer, p70S6K pathway, superoxide, zinc oxide nanoparticles
- MeSH Terms
-
- Apoptosis/drug effects*
- Carcinoma, Squamous Cell/metabolism*
- Caspases/metabolism
- Cell Death/drug effects
- Gingiva
- Gingival Neoplasms/metabolism*
- Humans
- Keratinocytes/metabolism
- Membrane Potential, Mitochondrial/drug effects
- Mitochondria/metabolism*
- Nanoparticles/chemistry*
- Oxidative Stress/drug effects
- Phosphorylation
- Reactive Oxygen Species/metabolism
- Ribosomal Protein S6 Kinases, 70-kDa/metabolism*
- Signal Transduction/drug effects*
- Zinc Oxide/pharmacology*
- PubMed
- 32111101 Full text @ Int. J. Mol. Sci.
Citation
L, S.W., Lee, C.H., Lin, M.S., Chi, C.W., Chen, Y.J., Wang, G.S., Liao, K.W., Chiu, L.P., Wu, S.H., Huang, D.M., Chen, L., Shen, Y.S. (2020) ZnO Nanoparticles Induced Caspase-Dependent Apoptosis in Gingival Squamous Cell Carcinoma through Mitochondrial Dysfunction and p70S6K Signaling Pathway. International Journal of Molecular Sciences. 21(5):.
Abstract
Zinc oxide nanoparticles (ZnO-NPs) are increasingly used in sunscreens, food additives, pigments, rubber manufacture, and electronic materials. Several studies have shown that ZnO-NPs inhibit cell growth and induce apoptosis by the production of oxidative stress in a variety of human cancer cells. However, the anti-cancer property and molecular mechanism of ZnO-NPs in human gingival squamous cell carcinoma (GSCC) are not fully understood. In this study, we found that ZnO-NPs induced growth inhibition of GSCC (Ca9-22 and OECM-1 cells), but no damage in human normal keratinocytes (HaCaT cells) and gingival fibroblasts (HGF-1 cells). ZnO-NPs caused apoptotic cell death of GSCC in a concentration-dependent manner by the quantitative assessment of oligonucleosomal DNA fragmentation. Flow cytometric analysis of cell cycle progression revealed that sub-G1 phase accumulation was dramatically induced by ZnO-NPs. In addition, ZnO-NPs increased the intracellular reactive oxygen species and specifically superoxide levels, and also decreased the mitochondrial membrane potential. ZnO-NPs further activated apoptotic cell death via the caspase cascades. Importantly, anti-oxidant and caspase inhibitor clearly prevented ZnO-NP-induced cell death, indicating the fact that superoxide-induced mitochondrial dysfunction is associated with the ZnO-NP-mediated caspase-dependent apoptosis in human GSCC. Moreover, ZnO-NPs significantly inhibited the phosphorylation of ribosomal protein S6 kinase (p70S6K kinase). In a corollary in vivo study, our results demonstrated that ZnO-NPs possessed an anti-cancer effect in a zebrafish xenograft model. Collectively, these results suggest that ZnO-NPs induce apoptosis through the mitochondrial oxidative damage and p70S6K signaling pathway in human GSCC. The present study may provide an experimental basis for ZnO-NPs to be considered as a promising novel anti‑tumor agent for the treatment of gingival cancer.
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