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.
Highlights
Oral squamous cell carcinoma is a malignant neoplasm and its high incidence and mortality rates are relevant in certain parts of Europe and South-Eastern Asia [1]
The growth inhibition of Zinc oxide nanoparticles (ZnO-NPs) in gingival cancer cells was more effective than other types of human cancer cell lines (Figure S1)
These results demonstrated that ZnO-NPs induce a selective anti-cancer effect against human gingival squamous cell carcinoma (GSCC)
Summary
Oral squamous cell carcinoma (oral cancer; OSCC) is a malignant neoplasm and its high incidence and mortality rates are relevant in certain parts of Europe and South-Eastern Asia [1]. The character of OSCC is a high degree of local infiltration and it has a high rate of recurrence and metastasis for the cervical lymph nodes [2,3]. Despite advances in diagnostic technology and treatment strategy, the prognosis of OSCC remains poor, especially in late stage. More than 60% of patients with OSCC have late-stage disease (stage III or IV) resulting from the difficult diagnosis, especially gingival squamous cell carcinomas (GSCC), which pretend as benign disease both clinically and histologically [4,5,6]. There is an urgent need to discover effective strategies for the treatment of human GSCC
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
