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
Highlights
Oral cancer initially originates as small lesion from tissues in the mouth, and subsequently grows to a cancerous mass in the oral cavity [1]
Tiazofurin suppressed the proliferative potential of the oral carcinoma cells in a concentrationdependent manner
The current study showed that tiazofurin markedly elevated caspase-3 and caspase -9 activities in SCC-VII and SCC-25 cells, relative to untreated cells
Summary
Oral cancer initially originates as small lesion from tissues in the mouth, and subsequently grows to a cancerous mass in the oral cavity [1]. The signals are generated due to aggregated misfolded proteins, irregularity in Ca2+ release, and protein processing in non-specific manner in endoplasmic reticulum [4] The activation of these stresses for prolonged durations serves as signal for induction of apoptosis [5]. The cells were separately seeded in 96-well plates, each at a density of 1 x 106 cells/well in DMEM and incubated for 24 h. The cells were seeded in 6-well plates, each at a density of 1 x 105 cells/well in DMEM, and were cultured for 24 h at 37 ̊C, followed by incubation for 48 h with 2.0 μM tiazofurin. Tiazofurin exhibited cytotoxic effect on the oral carcinoma cells by activating apoptosis
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