Purpose: To investigate the role of NF-kappaB signal transduction pathway in apoptosis induced by shikonin in human tongue squamous cell carcinoma Tca-8113 cell line.
Methods: Expression of IkappaBa, phosphatase-IkappaBa, bcl-2 and Bax proteins were detected by Western blot, NF-kappaB DNA-binding activity was detected by electrophoretic mobility shift analysis (EMSA), and activities of caspase 3, caspase 8 and caspase 9 were analyzed by enzyme linked immunosorbent assay(ELISA). The data was analyzed by one-way ANOVA test and t test using SPSS12.0 software package.
Results: The expression of phosphatase-IkappaBa protein and the nuclear NF-kappaB DNA-binding activity was significantly decreased in shikonin treated cells by Western and EMSA. Bcl-2 protein expression was also decreased in the process. The activity of all the three proteases was elevated and pancaspase inhibitor Z-Asp-CH2-DCB could protect Tca8113 cells from shikonin-induced apoptosis(P=0.02).
Conclusions: Anti-tumor effects of shikonin in Tca-8113 cells act at least partially through the inactivation of NF-kappaB pathway and subsequent activation of protease caspase family. Pharmacologic inhibition of the NF-kappaB activity by shikonin might be a powerful treatment option for OSCC.