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.

Curcumin is a widely used flavoring agent in food, and it has been reported to inhibit cell growth, to induce apoptosis, and to have antitumor activity in many cancers. Cisplatin is one of the most potent known anticancer agents and shows significant clinical activity against a variety of solid tumors. This study was undertaken to investigate the synergistic apoptotic effects of co-treatment with curcumin and cisplatin on human tongue SCC25 cells. To investigate whether the co-treatment efficiently reduced the viability of the SCC25 cells compared with the two treatments separately, an MTT assay was conducted. The induction and the augmentation of apoptosis were confirmed by DNA electrophoresis, Hoechst staining, and an analysis of DNA hypoploidy. Western blot, MMP and immunofluorescence tests were also performed to evaluate the expression levels and the translocation of apoptosis-related proteins following the co-treatment. In this study, following the co-treatment with curcumin and cisplatin, the SCC25 cells showed several forms of apoptotic manifestation, such as nuclear condensation, DNA fragmentation, reduction of MMP, increased levels of Bax, decreased levels of Bcl-2, and decreased DNA content. In addition, they showed a release of cytochrome c into the cytosol, translocation of AIF and DFF40 (CAD) to the nuclei, and activation of caspase-7, caspase-3, PARP, and DFF45 (ICAD). In contrast, separate treatments of 5 μM of curcumin or 4 μg/ml of cisplatin, for 24 hours, did not induce apoptosis. Therefore, our data suggest that combination therapy with curcumin and cisplatin could be considered as a novel therapeutic strategy for human oral squamous cell carcinoma.

Cruciferous vegetables including diindolylmethane (DIM) have been shown to have anticancer activity. Especially, DIM-pPhBr and DIM-pPhF used in this study was reported to have more effective and less toxic effects than DIM. However, there is no report presenting their anti-tumorigenic activity in oral cancer. In the present study, we examined the effects of DIM-pPhBr and DIM-pPhF on the cell proliferation and apoptosis in KB human oral cancer cells. DIM-pPhBr and DIM-pPhF decreased cell proliferation and induced apoptosis evidenced by western blot analysis, DAPI staining and sub-G1 population. This provides the first evidence that DIM-pPhBr and DIM-pPhF originating from cruciferous vegetables induce apoptotic cell death in human oral cancer cells to inhibit cancer cell proliferation.

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

This study was conducted to investigate the development and gene expression in miniature pig nuclear transfer (mNT) embryos produced under different osmolarity culture conditions. Control group of mNT embryos was cultured in PZM-3 for 6 days. Treatment group of mNT embryos was cultured in modified PZM-3 with NaCl (mPZM-3, 320 mOsmol) for 2 days, and then cultured in PZM-3 (270 mOsmol) for 4 days. Blastocyst formation rate of the treatment group was significantly higher than the control and the apoptosis rate was significantly lower in treatment group. Bax- and caspase-3 mRNA expression were significantly higher in the control than the treatment group. Also, the majority of imprinting genes were expressed aberrantly in in vitro produced mNT blastocysts compared to in vivo derived blastocyst H19 and Xist mRNA expression were significantly lower in the control than the treatment group or in vivo. IGF2 mRNA expression was significantly higher in the control than the treatment group or in vivo. IGF2r mRNA expression was significantly lower in the control. Methylation profiles of individual DNA strands in H19 upstream T-DMR sequences showed a similar methylation status between treatment group and in vivo. These results indicate that the modification of osmolarity in culture medium at early culture stage could provide more beneficial culture environments for mNT embryos.

Taxol(paclitaxel) is used in chemotherapy against several cancer. Treatment of tumor cell lines with taxol induces apoptosis, but exact mechanism is not sufficiently understood. The purpose of this study was to investigate apoptosis by the inhibitory effect of paclitaxel on the motility properties of human salivary gland adenocarcinoma cell lines. Paclitaxel inhibited cell motility induced by soluble and immobilized attractant. It suggested that paclitaxel would be a potent inhibitor of salivary gland adenocarcinoma cell motility independent of its cytotoxic and apoptotic activity.

AJthough salivary gland adenocarcinoma accounts for third prevalence rate of all salivary gland tumors. it is one of the most aggressive solid tumors. Current therapy does not s ignificantly improve survival rates. Thus‘ investigating new therape utic modali t ies aga inst sali va ry gland adenocarcinoma is necessary. Manumycin A. a natural product o{ Streptα7Jyces parvuJus‘ inhi bits farn esy l- transferase by competition with farnesyl pyrophosphate groups . Manumycin has shown antitumor activity in several ex per‘ imental systems through identifying the regulatory pathway of apoptosis. The hi erarchical relationship of caspase-8 to caspase-3 and caspase-9 in the drug-induced a poptosis pathway in antitumol effect is not clear. The hi erarchical relations hip between cytochrome c and the caspases and provided evidence to support the hypothesis that the release of cytochrome c was upstream of caspase activation in the enhanced apoptosis induced by manumycin A Manumycin A has not been examined extensively in human salivary gland tumor and has not yet been clarified. The purpose of this study were to investigate mRNA and protein expression of Bc l- 2 、Bax, Cytochrome C‘ caspase- 3 , 一8 and -9 in SGT cell line by RT-PCR and immunoslot blotting, and to a pply its results to exami ne iLs chemoprevention for salivary gland adenocarcinoma. MTI assay showed about 50% cellular viability of SGT cell line treated by 50μM manunycin A Bcl-2. Bax‘ and caspase-8 mRNA expression in SGT cell line were unchangeable after 50μM manu nycin A Cytochrome C‘ caspase-3 and -9 showed about 1.5-5 folds higher mRNA expression in SGT cell line than that of control a nd DMSO- t reated group a fter 50M manunycin A. Bcl-2, Bax, and caspase-8 protein expression in SGT ce ll line were unchangcable after 50μM manunycin A. Cy Lochrorne C, caspase-3 and -9 showed about 2-7 fo lds higher protein express ion in SGT cell line than that of control and DMSO-treated group after 50μM manunycin A. mRNA expression was assoc iated with protein expression in SGT cell line after 50μM manunycin A. It suggested that manumycin A would induce poptotic effect on SGT cell line by caspase-3 and - 9 activation through cytochrorne c release. And man umycin A will be a useful chemoprevention drug for human salivary gland carcinoma in future.

Adenocarcinoma NOS of salivary glands is characterized by a high rate of local recurrences and metastasis. Long-term survival rate of Adenocarcinoma NOS lis not promising. Thus, different chemotherapeutical approaches had been proposed for this neoplasm, including apoptosis induction by drugs. The current treatment of choice of adenocarcinoma NOS is controversible, and an effective treatment for them is not yet available. Chemotherpeutic agents that can be inhibit or reverse the tumor growth by targeting apoptotic pathways will be new candidates for cancer prevention and therapy. The purpose of this study were to study the effect of Brefeldin A(BFA) as apoptotic inducing agent in SGT cell line from human submandibular adenocarcinoma NOS and apply these results to make a plan of treatment and prognosis of salivary gland tumors involving adenocarcinoma NOS. SGT cells were treated with a 300μM BFA solution in serum-free medium during 18 hours. SGT cells were grown in DMEM with 10% fetal bovine serum served as controls. The growth curve and MTT assay for succinyl dehydrogenase activity were performed. For apoptotic analysis, fragmentation of genomic DNA was confirmed with gel electrophoresis. Transmission electron microscopy was assessed for the effect of BFA on SGT cells phenotype. Apoptotic cell recognition and counting were carried out with Annexin-V, caspase 3 and APo2.7 antibody through flow cytometry. Growth of SGT cell line was abrutply decreased after 1 day of BFA treatment. MTT assay for succinyl dehydrogenase activity of the cells showed about 55% after 300μM BFA treatment. Destruction of cellular organells, numerous vacuolation in the cytoplasm & nucleus, chromatin margination, & fragments of nucleus were seen with TEM after 300μM BFA treatment. DNA fragmentation of SGT cell line was induced by 300μM BFA treatment and confirmed by gel electrophoresis from genomic DNA extraction. Late apoptosis of the cells through flow cytometric analysis of Annexin-V staining as induced by 300μM BFA treatment. Early apoptosis of the cells through flow cytometric analysis of caspase 3 and Apo 2.7 staining was induced by 300μM BFA treatment. It suggested that early and late apoptosis of SGT cell line would be induced by Brefeldin A treatment in vitro study. This work evaluated the efficacy of BFA, a potent apoptosis inducer, on SGT cultured cell line. And BFA as chemotherapeutic agent will be used as the treatment choice for adenocarcinoam NOS, and be need to apply BFA to in vivo study & clinical approach in future.

Apoptosis has been regarded as a therapeutic target because apoptosis is typically disturbed in human cancer. Silymarin found in the seeds of the milk thistle (Silybum marianum) has been reported to exert anti-cancer properties through apoptosis. This study was performed to investigate the molecular target for silymarin-mediated apoptosis in human colorectal cancer cells. Silymarin reduced the cell viability and induced an apoptosis in human colorectal cancer cells. ATF3 overexpression increased PARP cleavage by silymarin. Increased ATF3 expression in both protein and mRNA was observed in silymarin-treated cells. In addition, silymarin increased the luciferase activity of ATF3 promoter. Inhibition of JNK and IκK-α blocked silymarin-mediated ATF3 expression. The results suggest that silymarin induces apoptosis through JNK and IκKα-dependent ATF3 expression in human colorectal cancer cells.