• 약학회지
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• 제51권4호
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• pp.239-245
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• 2007

In order to evaluate the genotoxicity of airborne particulate matter extracted with dichloromethane (APE), the rat microsome mediated (S-9) or DNA repair enzyme treated Comet assays were performed using the single cell gel electrophoresis in A549 human lung carcinoma cells. It was found that the cells interacting with APE showed more DNA single-strand breaks relative to untreated cells. The genotoxicity of APE was increased with the treatment of S-9 mixture. Microsome mediated DNA damage was inhibited by CYP1Al inhibitor, quercetin. The APE also showed oxidative DNA damage evaluated by endonuclease III treatment. Oxidative DNA damage of APE was inhibited by antioxidants such as vita- min C and Trolox. We also found that the vegetables or fruits extract may reduce APE-induced genotoxicity by their anti- oxidant activity and CYP1A1 inhibition.

• 한국발생생물학회지:발생과생식
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• 제27권2호
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• pp.77-89
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• 2023

Metformin is the most widely used anti-diabetic drug that helps maintain normal blood glucose levels primarily by suppressing hepatic gluconeogenesis in type II diabetic patients. We previously found that metformin induces apoptotic death in H4IIE rat hepatocellular carcinoma cells. Despite its anti-diabetic roles, the effect of metformin on hepatic de novo lipogenesis (DNL) remains unclear. We investigated the effect of metformin on hepatic DNL and apoptotic cell death in H4IIE cells. Metformin treatment stimulated glucose consumption, lactate production, intracellular fat accumulation, and the expressions of lipogenic proteins. It also stimulated apoptosis but reduced autophagic responses. These metformin-induced changes were clearly reversed by compound C, an inhibitor of AMP-activated protein kinase (AMPK). Interestingly, metformin massively increased the production of reactive oxygen species (ROS), which was completely blocked by compound C. Metformin also stimulated the phosphorylation of p38 mitogen-activated protein kinase (p38MAPK). Finally, inhibition of p38MAPK mimicked the effects of compound C, and suppressed the metformin-induced fat accumulation and apoptosis. Taken together, metformin stimulates dysregulated glucose metabolism, intracellular fat accumulation, and apoptosis. Our findings suggest that metformin induces excessive glucose-induced DNL, oxidative stress by ROS generation, activation of AMPK and p38MAPK, suppression of autophagy, and ultimately apoptosis.

• IMMUNE NETWORK
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• 제13권5호
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• pp.168-176
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• 2013

In the last few years major progress has been made in better understanding the role of natural killer (NK) cells in hepatitis C virus (HCV) infection. This includes multiple pathways by which HCV impairs or limits NK cells activation. Based on current genetic and functional data, a picture is emerging where only a rapid and strong NK cell response early on during infection which results in strong T cell responses and possible subsequent clearance, whereas chronic HCV infection is associated with dysfunctional or biased NK cells phenotypes. The hallmark of this NK cell dysfunction is persistent activation promoting ongoing hepatitis and hepatocyte damage, while being unable to clear HCV due to impaired IFN-${\gamma}$ responses. Furthermore, some data suggests certain chronically activated subsets that are $NKp46^{high}$ may be particularly active against hepatic stellate cells, a key player in hepatic fibrogenesis. Finally, the role of NK cells during HCV therapy, HCV recurrence after liver transplant and hepatocellular carcinoma are discussed.

• Journal of Chest Surgery
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• 제50권3호
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• pp.153-162
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• 2017

Background: The mesenchymal-epithelial transition factor (MET) receptor can be overexpressed in solid tumors, including small cell lung cancer (SCLC). However, the molecular mechanism regulating MET stability and turnover in SCLC remains undefined. One potential mechanism of MET regulation involves the C-terminus of Hsp70-interacting protein (CHIP), which targets heat shock protein 90-interacting proteins for ubiquitination and proteasomal degradation. In the present study, we investigated the functional effects of CHIP expression on MET regulation and the control of SCLC cell apoptosis and invasion. Methods: To evaluate the expression of CHIP and c-Met, which is a protein that in humans is encoded by the MET gene (the MET proto-oncogene), we examined the expression pattern of c-Met and CHIP in SCLC cell lines by western blotting. To investigate whether CHIP overexpression reduced cell proliferation and invasive activity in SCLC cell lines, we transfected cells with CHIP and performed a cell viability assay and cellular apoptosis assays. Results: We found an inverse relationship between the expression of CHIP and MET in SCLC cell lines (n=5). CHIP destabilized the endogenous MET receptor in SCLC cell lines, indicating an essential role for CHIP in the regulation of MET degradation. In addition, CHIP inhibited MET-dependent pathways, and invasion, cell growth, and apoptosis were reduced by CHIP overexpression in SCLC cell lines. Conclusion: C HIP is capable of regulating SCLC cell apoptosis and invasion by inhibiting MET-mediated cytoskeletal and cell survival pathways in NCI-H69 cells. CHIP suppresses MET-dependent signaling, and regulates MET-mediated SCLC motility.

• International Journal of Oral Biology
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• 제39권3호
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• pp.159-167
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• 2014

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 $5{\mu}M$ of curcumin or $4{\mu}g/ml$ 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.

• 대한한방내과학회지
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• 제18권1호
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• pp.191-206
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• 1997

In order to investingate the effects of Jukyeopseokgotanggagambang Extract on antitumor effects after human cell lines(A549, hep3B, Caki-1, Ehrlich) transplantation into the peritoneal cavity or right groin in mice induced by RPMI 1640 and GIBCO etc., the extracts of its herbal medicines were orally administered for 10 or 12days. Experimental studies were performed for measurance of antitumor effect of MMC(Mitomycin C) and lysosomal enzyme's activities using colony forming efficiency, SRB assay which were regarded as a valuable method for antitumor effects of unknown compound on tumor cell lines. The results obtained in this studies were as follows: 1. According to the change of colony-forming efficiency and SRB assay of Caki-1 cell, hep3B and A549 cells after exposure to the extract of Jukyeopseokgotanggagambang extract, that extract depressed the growth of tumor cells depending on its concentration. 2. Antitumor activities of the ethanol extract from Jukyeopseokgotanggagambang extract and MMC on ascites form of Ehrlich carcinoma in mice is a little improved. Especially mean survival times of the group of Jukyeopseokgotanggagambang extract 200mg/kg and MMC 0.1mg/kg is improved over 30%. 3. When Jukyeopseokgotanggagambang extract and MMC are administerated together, the weight of tumor is more decreased than MMC alone. 4. The effects of the Jukyeopseokgotanggagambang extract and MMC on the lysosomal enzymes in Ehrlich ascites carcinoma cell are more significantly improved than MMC alone. 5. Jukyeopseokgotanggagambang extract also increased the uptake of MMC into Ehrlich carcinoma cells. According to the above results, it could be suggested that Jukyeopseokgotanggagambang extract has indirect autitumor effects by strengthening the effects of MMC on tumor cells.

• 대한한방종양학회지
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• 제3권1호
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• pp.149-167
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• 1997

In order to investingate the effects of Jukyeopseokgotanggagambang Extract on antitumor effects after human cell lines(A549, hep3B, Caki-1, Ehrlich) transplantation into the peritoneal cavity or right groin in mice induced by RPMI 1640 and GIBCO etc., the extracts of its herbal medicines were orally administered for 10 or 12days. Experimental studies were performed for measurance of antitumor effect of MMC(Mitomycin C) and lysosomal enzyme's activities using colony forming efficiency, SRB assay which were regarded as a valuable method for antitumor effects of unknown compound on tumor cell lines. The results obtained in this studies were as follows: 1. According to the change of colony-forming efficiency and SRB assay of Caki-1 cell, hep3B and A549 cells after exposure to the extract of Jukyeopseokgotanggagambang extract, that extract depressed the growth of tumor cells depending on its concentration. 2. Antitumor activities of the ethanol extract from Jukyeopseokgotanggagambang extract and MMC on ascites form of Ehrlich carcinoma in mice is a little improved. Especially mean survival times of the group of Jukyeopseokgotang-gagambang extract 200mg／kg and MMC 0.1mg／kg is improved over 30%. 3. When Jukyeopseokgotanggagambang extract and MMC are administerated together, the weight of tumor is more decreased than MMC alone. 4. The effects of the Jukyeopseokgotanggagambang extract and MMC on the lysosomal enzymes in Ehrlich ascites carcinoma cell are more significantly improved than MMC alone. 5. Jukyeopseokgotanggagambang extract also increased the uptake of MMC into Ehrlich carcinoma cells. According to the above results. it could be suggested that Jukyeopseokgotanggagambang extract has indirect autitumor effects by strengthening the effects of MMC on tumor cells.

• 대한본초학회지
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• 제35권6호
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• pp.35-41
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• 2020

Objectives : The object of this study was to observe anticancer and immunomodulatory effects of Formosa plum aqueous extracts (PLe) on non-small cell lung carcinoma (squamous epithelial carcinoma), NCI-H520, xenograft Balb/c nu-nu nude mice. Method : Three different dosages of PLe, 50, 100 and 200 mg/kg were orally administered once a day for 28 days from 11 days after tumor cell inoculation. Five groups, each of seven mice per group were used in the present study as follows. Tumor volume and weights, serum interferon (IFN)-γ levels, serum IL-6 were observed with tumor mass and lymphatic organ histopathology to detect anticancer and immunomodulatory effects. Result : Although no meaningful changes on the tumor weights and volumes were observed after treatment of all three different dosages of PLe, decreases of tumor cell volumes in tumor masses were dose-dependently decreased mediated by increases of apoptosis among tumor cells by treatment of PLe 100 and 200 mg/kg as compared with tumor-bearing control. In addition, decreases on the body weight and gains were also demonstrated in tumor-bearing control with increases of serum IL-6 levels. Conclusion : The results obtained in this study suggest that over 50 mg/kg of PLe showed favorable immunomodulatory and anticachexic effects with anticancer effects in 100 and 200 mg/kg of PLe treated groups on the NCI-H520 cell xenograft. However, detail mechanism studies should be conducted in future with the screening of the biological active compounds in this herb.

• Genomics & Informatics
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• 제21권2호
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• pp.22.1-22.15
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• 2023

Kidney renal clear cell carcinoma (KIRC) is one of the most aggressive cancer type of the urinary system. Metastatic KIRC patients have poor prognosis and limited therapeutic options. Ankyrin 3 (ANK3) is a scaffold protein that plays important roles in maintaining physiological function of the kidney and its alteration is implicated in many cancers. In this study, we investigated differential expression of ANK3 in KIRC using GEPIA2, UALCAN, and HPA databases. Survival analysis was performed by GEPIA2, Kaplan-Meier plotter, and OS-kirc databases. Genetic alterations of ANK3 in KIRC were assessed using cBioPortal database. Interaction network and functional enrichment analyses of ANK3-correlated genes in KIRC were performed using GeneMANIA and Shiny GO, respectively. Finally, the TIMER2.0 database was used to assess correlation between ANK3 expression and immune infiltration in KIRC. We found that ANK3 expression was significantly decreased in KIRC compared to normal tissues. The KIRC patients with low ANK3 expression had poorer survival outcomes than those with high ANK3 expression. ANK3 mutations were found in 2.4% of KIRC patients and were frequently co-mutated with several genes with a prognostic significance. ANK3-correlated genes were significantly enriched in various biological processes, mainly involved in peroxisome proliferator-activated receptor (PPAR) signaling pathway, in which positive correlations of ANK3 with PPARA and PPARG expressions were confirmed. Expression of ANK3 in KIRC was significantly correlated with infiltration level of B cell, CD8+ T cell, macrophage, and neutrophil. These findings suggested that ANK3 could serve as a prognostic biomarker and promising therapeutic target for KIRC.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제44권6호
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• pp.282-288
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• 2018

Objectives: The purpose of this study was to evaluate the neck node metastasis pattern and related clinical factors in oral cavity cancer patients. Materials and Methods: In total, 76 patients (47 males, 29 females) with oral squamous cell carcinoma (OSCC) who had no previous malignancies and were not undergoing neoadjuvant concomitant chemoradiotherapy or radiotherapy were selected for analysis. Results: Occult metastases were found in 8 of 52 patients with clinically negative nodes (cN0, 15.4%). Neck node metastases were found in 17 patients (22.4%). There was a statistically significant relationship between neck node metastasis and T stage (P=0.014) and between neck node metastasis and distant metastasis (Fisher's exact test, P=0.019). Conclusion: Neck node metastasis was significantly related to tumor size and distant metastasis during follow-up.