ZnO Nanoparticles Induced Caspase-Dependent Apoptosis in Gingival Squamous Cell Carcinoma through Mitochondrial Dysfunction and p70S6K Signaling Pathway
學年 108
學期 2
出版（發表）日期 2020-02-26
作品名稱 ZnO Nanoparticles Induced Caspase-Dependent Apoptosis in Gingival Squamous Cell Carcinoma through Mitochondrial Dysfunction and p70S6K Signaling Pathway
作品名稱（其他語言）
著者 Shih-Wei Wang; Chien-Hsing Lee; Ming-Shen Lin; Chih-Wen Chi; Yu-Jen Chen; Guo-Shou Wang; Kuang-Wen Liao; Li-Pin Chiu; Shu-Hui Wu; Dong-Ming Huang; Luke Chen; Yung-Shuen Shen
單位
出版者
著錄名稱、卷期、頁數 International Journal of Molecular Science 21(5), 1612
摘要 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 oligonucleosomalDNAfragmentation. 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 Int. J. Mol. Sci. 2020, 21, 1612; doi:10.3390/ijms21051612 www.mdpi.com/journal/ijms Int. J. Mol. Sci. 2020, 21, 1612 2 of 16 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 e ect 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.
關鍵字 zinc oxide nanoparticles;gingival cancer;superoxide;p70S6K pathway
語言 en
ISSN 1422-0067
期刊性質 國外
收錄於 SCI
產學合作
通訊作者 Shih-WeiWang
審稿制度 是
國別 CHE
公開徵稿
出版型式 ,電子版
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