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dc.contributor.authorWang, Shih-Weien_US
dc.contributor.authorLee, Chien-Hsingen_US
dc.contributor.authorLin, Ming-Shenen_US
dc.contributor.authorChi, Chih-Wenen_US
dc.contributor.authorChen, Yu-Jenen_US
dc.contributor.authorWang, Guo-Shouen_US
dc.contributor.authorLiao, Kuang-Wenen_US
dc.contributor.authorChiu, Li-Pinen_US
dc.contributor.authorWu, Shu-Huien_US
dc.contributor.authorHuang, Dong-Mingen_US
dc.contributor.authorChen, Lukeen_US
dc.contributor.authorShen, Yung-Shuenen_US
dc.date.accessioned2020-05-05T00:02:18Z-
dc.date.available2020-05-05T00:02:18Z-
dc.date.issued2020-03-01en_US
dc.identifier.urihttp://dx.doi.org/10.3390/ijms21051612en_US
dc.identifier.urihttp://hdl.handle.net/11536/154102-
dc.description.abstractZinc 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.en_US
dc.language.isoen_USen_US
dc.subjectzinc oxide nanoparticlesen_US
dc.subjectgingival canceren_US
dc.subjectsuperoxideen_US
dc.subjectp70S6K pathwayen_US
dc.titleZnO Nanoparticles Induced Caspase-Dependent Apoptosis in Gingival Squamous Cell Carcinoma through Mitochondrial Dysfunction and p70S6K Signaling Pathwayen_US
dc.typeArticleen_US
dc.identifier.doi10.3390/ijms21051612en_US
dc.identifier.journalINTERNATIONAL JOURNAL OF MOLECULAR SCIENCESen_US
dc.citation.volume21en_US
dc.citation.issue5en_US
dc.citation.spage0en_US
dc.citation.epage0en_US
dc.contributor.department生物科技學系zh_TW
dc.contributor.department分子醫學與生物工程研究所zh_TW
dc.contributor.departmentDepartment of Biological Science and Technologyen_US
dc.contributor.departmentInstitute of Molecular Medicine and Bioengineeringen_US
dc.identifier.wosnumberWOS:000524908500063en_US
dc.citation.woscount0en_US
Appears in Collections:Articles