Terfenadine (TFN) was a second generation histamine receptor antagonist. Although several studies have reported the regulatory effect of H1-histamine receptor antagonists in human cancer cell lines, its effect in oral cancer remains unclear. In this study, we focused on addressing the anti-cancer activity of TFN in human oral cancer cell lines. The anti-cancer activities of TFN were performed by tryphan blue exclusion assay, 4'-6-diamidino-2-phenylindole (DAPI) staining, live/dead assay and Western blot analysis. TFN induced a significant reduction of the growth in three different human oral cancer cell lines (MC3, HSC4 and Ca9.22). TFN markedly induced apoptosis through DNA damage and increase in cytotoxicity. It also accumulated cleaved PARP and caspase 3. This process was due to cleavage of caspase 8 and Bid protein. The results from this study strongly demonstrated that the cleavages of caspase 8 and Bid are required for the apoptotic activity of TFN in human oral cancer cells. Taken together, these findings suggest TFN as a potent anticancer drug candidate for the treatment of oral cancer.

Caffeic acid phenethyl ester (CAPE), a component of propolis, was reported to possess anti-inflammatory, anti-bacterial, anti-viral, and anti-tumor activities. Our aim was to investigate the effect of CAPE on apoptosis in cultured human mucoepidermoid carcinoma (MEC) cell line, MC-3. Apoptotic effects of CAPE were measured by cell viability assays, Western blotting, 4’-6-diamidino-2-phenylindole (DAPI) staining and Live/Dead assay. The result of cell viability assay showed that CAPE displayed a strong growth-inhibitory effect in a concentration-dependent manner against MC-3 cells. Consumption of CAPE resulted in pronounced increase in the cleavage of caspase-3 and PARP, induced nuclear condensation and fragmentation and clearly increased the number of dead cells in MC-3 cells. CAPE also caused the increase in truncated Bid (t-Bid) and the cleavage of caspase-8 and this phenomenon was regulated by death receptor 5 (DR5). In addition, Phosphorylation of AKT and ERK were downregulated by CAPE. Taken together, these results suggest that CAPE is a potent apoptosis-inducing agent in MC-3 cells.

Background. Vitamin K (VK) is a fat-soluble vitamin and is known to have anticancer activity in various cancer cell lines. However, there is no report on the anticancer effect of VK2 in mucoepidermoid carcinoma cells. Methods. The effects of VK2 on anti-proliferative and apoptotic activity were recognized by the trypan blue exclusion assay, 4'-6-diamidino-2-phenylindole (DAPI) staining and Western blot analysis. Results. The results showed that VK2 decreased cell viability and induced apoptotic programmed cell death in MC3 cells evidenced by the cleavages of caspase3 and PARP. VK2 treatment clearly increased Bak and truncated Bid (t-Bid) compared with the control treatment whereas it did not alter other Bcl-2 family members. Conclusions. Overall, our results suggest that VK2 can be a good apoptotic inducer accompanied by the increase in Bak and Bid protein. VK2 may be a potent target of anticancer drug candidate for the treatment of oral cancer.

Dibenzylideneacetone (DBA), an analogue of curcumin has been shown to have anti-cancer activity in a variety of tumor cell lines. However, the anti-cancer activity of DBA and its molecular mechanism in HN22 oral cancer cell line have not been fully explored. The effects of DBA on anti-proliferative and apoptotic activity were evaluated by the trypan blue exclusion assay, 4’-6-diamidino-2-phenylindole (DAPI) staining, Western blot analysis, and reverse transcriptase-polymerase chain Reaction (RT-PCR). Our data showed that the treatment of DBA to HN22 cells exerted anti-proliferative and apoptotic activities and the activity was accompanied by a decrease in Sp1 protein, Sp1 mRNA and its promoter activity. DBA also reduced the expression level of Sp1 protein and caused apoptotic cell death in HN22 cells simultaneouly. Phosphorylation of ERK and JNK were regulated by DBA whereas phosphorylation of p38 was not altered. Overall, our results suggest that the regulation of Sp1 activities and ERK/JNK are involved in DBA-induced apoptosis and DBA can be a promising anticancer drug candidate for the treatment of oral cancer.

β-phenylethyl isothiocyanate(PEITC) is a component derived from cruciferous vegetables and has been demonstrated to fight many types of cancers through various molecular pathways. In the present study, we focused on its effect on the induction of apoptotic cell death to inhibit cell growth and its molecular mechanism in HSC-4 human oral cancer cells. A colorimetric MTS assay was used to examine cell viability. The apoptotic effect and was investigated using DAPI staining and the molecular target and mechanism of PEITC-mediated apoptosis were determined by Western blotting. The result showed that PEITC inhibited oral cancer cell growth and induced apoptosis via extrinsic signaling pathway evidenced by the activation of caspase 8, truncation of bid protein and induction of death receptor(DR) 5. DR5 protein level was increased through the activation of p38 and c-Jun N-terminal kinase(JNK). These results from this study strongly suggest that DR5 is a potential molecular target for PEITC-induced apoptosis in oral cancer via p38 and JNK.

Runt-related transcription factor (RUNX) 3 is well known as a developmental regulators, as well as candidate tumor suppressor gene in human breast cancer, gastric cancer, esophageal cancer, and so on. The present study was aimed to analyze the expression of RUNX3 protein in oral squamous cell carcinoma (OSCC) from Korean patients. The immunohistochemical stain was performed with 14 normal oral mucosa (NOM) and 25 OSCCs, and statistical analysis was carried out to find out the correlation between the expression of RUNX and clinicopathological parameters of OSCC patients. In OSCC, the expression of RUNX3 protein was found to increase more than in NOM. Moreover, in the univariate correlation analysis, the gender, regional lymph node metastasis, and histopathologic differentiation of OSCC patients were positively correlated with the expression of RUNX3 (p<0.05). These results indicate that RUNX3 can play a role as an oncogene in OSCC, in contrast to some reports on RUNX3 in other human cancers. In addition, RUNX3 may be considered as new malignant biomarker of OSCC.

Emodin is a bioactive compound isolated from the root and rhizomes of Rheum plamatum L. (polygenaceae), which is known as a traditional Chinese and Japanese medicine. In the present study, the effect of emodin on YD-15 mucoepidermoid carcinoma cells and its molecular mechanism were investigated. This study shows that emodin significantly inhibits the growth of YD-15 cells. Activation of caspase-3 and PARP is triggered by emodin and it increases sub-G1 population and the number of YD-15 cells with nuclear condensation and fragmentation. In addition, we found that emodin significantly decreases myeloid cell leukemia 1(MCL-1). These results suggest that MCl-1 is an important molecule for emodin-induced apoptosis. Taken together, emodin inhibits cell viability and induces apoptosis via down-regulation of MCL-1 and it can be a new potent anticancer drug candidate for the treatment of mucoepidermoid carcinoma

The human embryonic-lethal abnormal vision-like protein, HuR, stabilizes mRNA containing adenine- and uridine- rich elements in their 3’untranslated region. Because cyclooxygenase-2 (COX-2) mRNA is a cellular transcript that contains an adenine- and uridine-rich element, it can be regulated by the HuR protein. In this study, we examined the relationship between COX-2, HuR, MVD, and the clinicopathological parameters. Nineteen out of 43 cases of HNSCC showed high level of COX-2expression, and 68% of these patients showed high COX-2 immuno-reactivity indicating the strong expression of the cytoplasmic HuR protein. Also, MVD expression in the cases with high COX-2 expression was higher than in the cases with low COX-2 expression. These results suggest a strong correlation between the overexpression of cytoplasmic HuR and COX-2 expression in HNSCC, and that COX-2 is associated with MVD in HNSCC. In conclusion, COX-2 regulated by cytoplasmic HuR may be a good tumor angiogenic factor in HNSCC.