Tiazofurin inhibits oral cancer growth in vitro and in vivo via upregulation of miR-204 expression

Abstract

Purpose: To investigate the effect of tiazofurin on proliferation and growth of oral cancer cells, and the associated mechanism(s) of action.Methods: The effect of tiazofurin on the cytotoxicity of SCC-VII and SCC-25 oral cancer cells were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, while cell apoptosis was determined by flow cytometry. Western blotting was used for assaying proteinexpressions.Results: Tiazofurin inhibited the viability of the oral cancer cells in a concentration-based manner (p < 0.05). Tiazofurin treatment at a dose of 2.0 μM reduced the proliferation of SCC-VII and SCC-25 cells to 25 and 22 %, respectively. Apoptosis was significantly increased in SCC-VII and SCC-25 cells by tiazofurin treatment, relative to untreated cells (p < 0 .05). Tiazofurin also increased the activation levels of caspase-3 and caspase-9 and downregulated the expressions of p-Akt and p-mTOR in the two cancer cell lines. Moreover, miR-204 expression was significantly promoted in the tiazofurin-treated cells, when compared to control (p < 0 .05). In SCC-VII cells, treatment with tiazofurin suppressed Factin expression, relative to control.Conclusion: These results demonstrate that tiazofurin inhibits the viability and proliferation of SCC-VII and SCC-25 cancer cells via induction of apoptosis and activation of caspase-3/caspase-9. Moreover, tiazofurin targets Akt/mTOR pathway, and upregulats the expressions of F-actin and miR-204 in the oral carcinoma cells. These findings suggest that tiazofurin has a potential for use as an effective treatment for oral cancer. Keywords: Oral cancer, Tiazofurin, Apoptosis, Caspase, Cytotoxicity