IADR Abstract Archives
Aurora Kinase Inhibitor-induced Cytotoxicity in Oral Cancer Cells
Objectives: Aurora kinases, particularly Aurora-A and Aurora-B, are up-regulated in various human cancers including oral cancer. Therefore, many studies have considered them as potential prognostic markers and targets for cancer treatment. This study aimed to investigate the expression levels of Aurora-A and Aurora-B in p53-mutated oral squamous cell carcinoma (OSCC) cell lines ORL-48T and ORL-136T and to investigate the cytotoxic effect of Aurora kinase inhibitor in both cell lines.
Methods: The expression levels of Aurora-A and Aurora-B in ORL-48T and ORL-136T as well as in normal human gingival epithelial cells (HGEP) were examined by real-time RT-PCR and Western blot analysis. The MTT assay was performed to examine the cytotoxicity of pan-Aurora kinase inhibitor (CCT137690) in ORL-48T and ORL-136T.
Results: ORL-136T, but not ORL-48T, expressed a significant increase in mRNA and protein levels of Aurora-A as compared to HGEP. Although ORL-136T did not demonstrate a significantly increased level of Aurora-B mRNA, this cell line demonstrated a remarkable higher level of Aurora-B protein than ORL-48T and HGEP. The MTT assay showed that ORL-48T cells were more sensitive to the treatment by CCT137690 as compared with ORL-136T. At 48 h post-treatment with CCT137690 at concentrations of 10 µM, the cell viability of ORL-48T were significantly reduced as compared to those of ORL-136T (p<0.05). At 72 h post-treatment, the cell viability of ORL-136T was approximately 75% while ORL-48T demonstrated less than 10% survival.
Conclusions: A pan-Aurora kinase inhibitor can induce a cytotoxicity in p53-mutated OSCC cell line ORL-48T but shows less cytotoxicity in ORL-136T which overexpressed Aurora-A and Aurora-B.
Methods: The expression levels of Aurora-A and Aurora-B in ORL-48T and ORL-136T as well as in normal human gingival epithelial cells (HGEP) were examined by real-time RT-PCR and Western blot analysis. The MTT assay was performed to examine the cytotoxicity of pan-Aurora kinase inhibitor (CCT137690) in ORL-48T and ORL-136T.
Results: ORL-136T, but not ORL-48T, expressed a significant increase in mRNA and protein levels of Aurora-A as compared to HGEP. Although ORL-136T did not demonstrate a significantly increased level of Aurora-B mRNA, this cell line demonstrated a remarkable higher level of Aurora-B protein than ORL-48T and HGEP. The MTT assay showed that ORL-48T cells were more sensitive to the treatment by CCT137690 as compared with ORL-136T. At 48 h post-treatment with CCT137690 at concentrations of 10 µM, the cell viability of ORL-48T were significantly reduced as compared to those of ORL-136T (p<0.05). At 72 h post-treatment, the cell viability of ORL-136T was approximately 75% while ORL-48T demonstrated less than 10% survival.
Conclusions: A pan-Aurora kinase inhibitor can induce a cytotoxicity in p53-mutated OSCC cell line ORL-48T but shows less cytotoxicity in ORL-136T which overexpressed Aurora-A and Aurora-B.