• BMB Reports
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• v.45 no.9
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• pp.526-531
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• 2012

Many malignant tumors become resistant to tumor necrosis factor-alpha (TNF-${\alpha}$)-induced cell death during carcinogenesis. In the present study, we examined whether parkin acts as a tumor suppressor in HeLa cells, a human cervical cancer cell line resistant to TNF-${\alpha}$-induced cell death. TNF-${\alpha}$-treatment alone did not affect HeLa cell viability. However, expression of parkin restored TNF-${\alpha}$-induced apoptosis in HeLa cells. Increased cell death was due to the activation of the apoptotic pathway. Expression of parkin in TNF-${\alpha}$-treated HeLa cells stimulated cleavage of the pro-apoptotic proteins caspase-8, -9, -3, -7 and poly ADP ribose polymerase (PARP). In addition, parkin expression resulted in decreased expression of the caspase inhibitory protein, survivin. These results suggest that parkin acts as a tumor suppressor in human cervical cancer cells by modulating survivin expression and caspase activity. We propose that this pathway is a novel molecular mechanism by which parkin functions as a tumor suppressor.

• The Journal of Korean Medicine
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• v.36 no.4
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• pp.19-34
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• 2015

Objectives: This study was performed to investigate the anti-tumor effect of O. japonicus extracts on intrahepatic cholangiocarcinoma cell line SNU-1079. Methods: Cholangiocarcinoma SNU-1079 cells were treated with various concentrations of O. japonicus DW and EtOH extracts ($0-300{\mu}g/ml$) for 24, 48 or 72 h. Cell viability was evaluated through a PMS/MTS assay, and the apoptosis rate was examined through ELISA assay and flow cytometry analysis. The mRNA expression of apoptosis- and cell cycle progression-related genes (Bcl-2, Mcl-1, Bax, Survivin, Cyclin D1, and p21) was evaluated using real-time PCR, and the caspase activity was examined using immunoblot analysis. Results: O. japonicus extracts inhibited cell proliferation and increased apoptosis rate in both ELISA assay and flow cytometry analysis. O. japonicus extracts decreased Bcl-2, Mcl-1, Survivin, and Cyclin D1 mRNA expression and increased Bax mRNA level. O. japonicus extracts also increased Caspase-3 activation. Overall, O. japonicus DW extracts were more effective than EtOH extracts. Conclusions: O. japonicus inhibited cell proliferation and induced apoptosis in SNU-1079 cells via mitochondria -mediated intrinsic pathway, which leads to Caspase-3 activation. The results indicate that O. japonicus is a potential therapeutic herb with anti-tumor effect against intrahepatic cholangiocarcinoma.

• Journal of Convergence for Information Technology
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• v.10 no.6
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• pp.209-216
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• 2020

Protein antigens and their epitopes are targets for epitope based vaccines. There are many prediction servers which can be used for identification of binding peptides to MHC molecules. However, choosing of appropriate prediction servers is difficult. This study compared data obtained from prediction servers and evaluate them in scope of binding affinity to MHC-I molecules. Here we predicted HLA-A2-restricted cytotoxic T lymphocyte epitopes from survivin as a potential target for multiple myeloma. We suggest a procedure for prediction of antigenic peptides which could bind to MHC-I molecule. The results of this study will assist researchers in selection and prediction of noble antigenic peptides.

• Molecules and Cells
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• v.41 no.9
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• pp.830-841
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• 2018

Recent studies have indicated that microRNAs (miRNAs) play an important role in hepatocellular carcinoma (HCC) progression. In this study, we showed that miR-766-3p was decreased in approximately 72% of HCC tissues and cell lines, and its low expression level was significantly correlated with tumour size, TNM stage, metastasis, and poor prognosis in HCC. Ectopic miR-766-3p expression inhibited HCC cell proliferation, colony formation, migration and invasion. In addition, we showed that miR-766-3p repressed Wnt3a expression. A luciferase reporter assay revealed that Wnt3a was a direct target of miR-766-3p, and an inverse correlation between miR-766-3p and Wnt3a expression was observed. Moreover, Wnt3a up-regulation reversed the effects of miR766-3p on HCC progression. In addition, our study showed that miR-766-3p up-regulation decreased the nuclear ${\beta}-catenin$ level and expression of Wnt targets (TCF1 and Survivin) and reduced the level of MAP protein regulator of cytokinesis 1 (PRC1). However, these effects of miR-766-3p were reversed by Wnt3a up-regulation. In addition, PRC1 upregulation increased the nuclear ${\beta}-catenin$ level and protein expression of TCF1 and Survivin. iCRT3, which disrupts the ${\beta}-catenin-TCF4$ interaction, repressed the TCF1, Survivin and PRC1 protein levels. Taken together, our results suggest that miR-766-3p down-regulation promotes HCC cell progression, probably by targeting the Wnt3a/PRC1 pathway, and miR-766-3p may serve as a potential therapeutic target in HCC.

• 대한생식의학회:학술대회논문집
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• 2005.11a
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• pp.101.1-101.1
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• 2005

• The Journal of Korean Medicine
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• v.37 no.1
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• pp.62-76
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• 2016

Objectives: The goal of this study was to investigate the anti-lipogenic effects of Samhwangsasim-tang(SHT), Daehwanghwangryunsasim-tang(DHT) aqueous extract on HepG2 cells with palmitate. Materials and Methods: HepG2 cells treated with palmitate were used in this study as hepatic steatosis model. Cells were treated with different concentrations of SHT, DHT aqueous extract for 24 hours. Cell viability and cytotoxicity were analyzed by MTT assay. Expressions of Bcl-2, Bax, Survivin, P21, TGF-${\beta}1$, LXR-${\alpha}$, ChREBP, ACC1, SCD1 mRNA were determined by Real-time PCR. Apoptosis of cells was detected by ELISA and FACS. Expression level of caspase-3 was studied by Western blot. Lipid accumulation was indicated by Oil Red O staining. Results: SHT, DHT aqueous extract had no cytotoxicity, but decreased palmitate-induced lipid accumulation in HepG2 cells. SHT aqueous extract suppressed fatty acid synthesis by inhibiting LXR-${\alpha}$, ChREBP, SCD1 activation and increasing TGF-${\beta}1$ expression level. DHT aqueous extract also suppressed fatty acid synthesis by decreasing ChREBP expression and increasing TGF-${\beta}1$ expression. Apoptosis of lipid accumulated cells was increased by enhanced activities of P21, caspase-3 and inhibited expressions of Bcl-2, Survivin. Conclusions: These results suggest that SHT and DHT have an anti-lipogenic effects on lipid accumulation of hepatic cell. Also SHT and DHT have an efficacy to increase apoptosis of adipocyte without cytotoxicity. Therefore, SHT and DHT might have potential clinical applications for treatment of hepatic steatosis.

• Journal of Microbiology and Biotechnology
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• v.24 no.6
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• pp.756-764
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• 2014

Apoptin, a chicken anemia virus-encoded protein, induces apoptosis in chicken or human tumor cells, localizing in their nuclei as opposed to the cytoplasm of non-transformed cells. The present study was undertaken to investigate whether ABPs1 could potentiate apoptin-induced apoptosis in HeLa cells. ABPs1 and the apoptin genes were successfully cloned into pIRES2-EGFP expression vector and expressed in HeLa cells. We report that ABPs1 augments apoptin cell growth inhibition in a concentration- and time-dependent manner. The DAPI staining and scanning electron microscopy observations revealed apoptotic bodies and plasma membrane pores, which were attributed to apoptin and ABPs1, respectively. Further, ABPs1 in combination with apoptin was found to increase the expression of Bax and to decrease the expression of survivin compared with either agent alone or the control. The apoptotic rate of HeLa cells treated with ABPs1 and apoptin in combination for 48 h was 53.95%. The two-gene combination increased the caspase-3 activity of HeLa cells. Taken together, our study suggests that ABPs1 combined with apoptin significantly inhibits HeLa cell proliferation, and induces cell apoptosis through membrane defects, up-regulation of Bax expression, down-regulation of survivin expression, and activation of the caspase-3 pathway. Thus, the combination of ABPs1 and apoptin could serve as a means to develop novel gene therapeutic agents against human cervical cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6791-6798
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• 2014

Background: To investigate the effect of silibinin on proliferation and apoptosis in human gastric cancer cell line MGC803 and its possible mechanisms. Materials and Methods: Human gastric cancer cell line MGC803 cells were treated with various concentration of silibinin. Cellular viability was assessed by CCK-8 assay andapoptosis and cell cycle distribution by flow cytometry. Protein expression and mRNA of STAT3, and cell cycle and apoptosis regulated genes were detected by Western blotting and real-time polymerase chain reaction, respectively. Results: Silibinin inhibits growth of MGC803 cells in a dose- and time-dependent manner. Silibinin effectively induces apoptosis of MGC803 cells and arrests MGC803 cells in the G2/M phase of the cell cycle, while decreasing the protein expression of p-STAT3, and of STAT3 downstream target genes including Mcl-1, Bcl-xL, survivin at both protein and mRNA levels. In addition, silibinin caused an increase in caspase 3 and caspase 9 protein as well as mRNA levels. Silibinin caused G2/M phage arrest accompanied by a decrease in CDK1 and Cyclin B1 at protein and mRNA levels.. Conclusions: These results suggest that silibinin inhibits the proliferation of MGC803 cells, and it induces apoptosis and causes cell cycle arrest by down-regulating CDK1, cyclinB1, survivin, Bcl-xl, Mcl-1 and activating caspase 3 and caspase 9, potentially via the STAT3 pathway.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1553-1564
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• 2016

Identification of novel therapeutics in glioblastoma remains crucial due to the devastating and infiltrative capacity of this malignancy. The current study was aimed to appraise effect of arsenic trioxide (ATO) in U87MG cells. The results demonstrated that ATO induced apoptosis and impeded proliferation of U87MG cells in a dose-dependent manner and also inhibited classical NF-${\kappa}B$ signaling pathway. ATO further upregulated expression of Bax as an important proapoptotic target of NF-${\kappa}B$ and also inhibited mRNA expression of survivin, c-Myc and hTERT and suppressed telomerase activity. Moreover, ATO significantly increased adhesion of U87MG cells and also diminished transcription of NF-${\kappa}B$ down-stream targets involved in cell migration and invasion, including cathepsin B, uPA, MMP-2, MMP-9 and MMP-14 and suppressed proteolytic activity of cathepsin B, MMP-2 and MMP-9, demonstrating a possible mechanism of ATO effect on a well-known signaling in glioblastoma dissemination. Taken together, here we suggest that ATO inhibits survival and invasion of U87MG cells possibly through NF-${\kappa}B$-mediated inhibition of survivin and telomerase activity and NF-${\kappa}B$-dependent suppression of cathepsin B, MMP-2 and MMP-9.

• Journal of Food Hygiene and Safety
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• v.26 no.2
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• pp.150-153
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• 2011

Betulinic acid (BA), a naturally occurring triterpene found in the bark of the white birch tree, has been investigated to induce apoptosis in various cancer cells and animal models. However, there is no report of the chemopreventive effect of BA in cervical cancer cells. Using KB human cervical cancer cells as a model, we currently show that BA decreases cell viability and induces apoptotic cell death. The mechanism of the BA-induced anti-growth response in KB cells is due to the down-regulation of specificity protein 1 (Sp 1) and its downstream targets, myeloid cell leukemia-1(Mcl-1) and survivin. Thus, BA acts as a novel chemopreventive agent through the regulation of Sp1 that is highly expressed in tumors.