• Preventive Nutrition and Food Science
• /
• 제4권4호
• /
• pp.260-264
• /
• 1999

Korean traditional fermented soy paste (doenjang) prolonged the life span of Balb/c mice injected with the sarcoma-180 cells. The activities of liver enzymes, such as xanthine oxidase, aminopyrine N-demethylase, aniline hydroxylase, ${\gamma}$-glutamylcysteine synthetase, glutathione reductase and glutathione S-transferase (GST), and the contents of lipid peroxide and glutathione were determined from the sarcoma-180 cell injected mice that were treated with methanol extracts from doenjang, miso and soybean. The content of lipid peroxide and the activity of xanthine oxidase in the liver of Balb/c mice which were increased by the transplantation of the sarcoma-180 cells were decreased by treatment with the methanol extract from doenjang. But the activities of aminopyrine N-dementhylase and aniline hydroxylase were not affected by the treatment of methanol extracts from doenjang to the mice injected with the sarcoma-180 cells. The content of glutathione, the activities of glutamylcysteine synthetase, glutathione reductase and glutathione S-transferase decreased by the injection of the sarcoma-180 were recovered considerably by the treatment of the methanol extract from doenjang.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권14호
• /
• pp.5529-5533
• /
• 2014

Background: The aim of this study was to investigate the effect of a c-myc antisense oligodeoxynucleotide and 5-fluorouracil on the expression of c-myc, invasion and proliferation of HEPG-2 liver cancer cells. Materials and Methods: HEPG-2 cells were treated with lipiosome-mediated c-myc ADSON and 5-fluorouracil. The proliferation inhibition rate and invasion were measured by MTT and invasion assay, respectively. Cell apoptosis was detected by flow cytometry and expression of c-myc by RT-PCR and immunohistochemistry. Results: The proliferation inhibition rate was significantly higher in the antisense oligodeoxynucleotide added-5-fluorouracil group than single antisense oligodeoxynucleotide or 5-fluorouracil group (p<0.05). G0/G1 cells in the antisense oligodeoxynucleotide group and S cells in the 5-fluorouracil groups were significantly increased than that in the control group, respectively (P<0.01). The amplification strips of PCR products in 5-FU, ASODN and combination groups were significantly weaker than that in the control group (P<0.01). The percentage of c-myc-protein-positive cells were significantly lower in antisense oligodeoxynucleotide, 5-fluorouracil and combination groups than that in the control group (P<0.01). Conclusions: A liposome-mediated c-myc antisense oligodeoxynucleotide and 5-fluorouracil can inhibit the proliferation and invasion of liver cancer cells by reducing the expression of c-myc. A c-myc antisense oligodeoxynucleotide can increase the sensitivity of liver cancer cells to 5-fluorouracil and decrease the dosage of the agent necessary for efficacy, providing an experimental basis for the clinical therapy of liver cancer.

• 한국미생물·생명공학회지
• /
• 제22권4호
• /
• pp.368-372
• /
• 1994

Three more unusual macrolides in addition to concnamycin B were isolated from the mycelium of Streptomyces sp. strain Bal6. These four compounds showed a potent cytotoxity to hunian cancer cell lines, SNU-1 (stomach cancer cell line), SNU-354 (liver cancer cell line), MCF- 7 (breast cancer cell line) and KB-3-1 (oral epidermoid carcinoma cell line). Interestingly, these compounds confered slight differential cytotoxity on RHEK-1, a human epidermal keratinocyte cell line immotalized by AD12-SV40 hybrid virus and RHEK-1/pSV$_{2}$ ras which was resulted from H-ras transfomation of RHEK-1. These compounds were determined to be concanamycin A, conca- namycin E and 0-methyl concanamycin B by NMR and other spectral analysis.

• 대한본초학회지
• /
• 제22권4호
• /
• pp.187-199
• /
• 2007

Objectives : The present study purposed to compare the antioxidant effect, anti inflammatory effect and cancer cell multiplication inhibition effect of Fructificatio Inonoti Obliqui aqueous extract according to extraction temperature. Methods : We medicated animal models, which had experimental oxidation, with Fructificatio Inonoti Obliqui total extract and $50^{\circ}C$ low temperature leachate, and performed hematological analysis and blood chemical analysis with measuring SOD, GSH, catalase, NO and MDA content in the liver. In addition, we made comparative observation of anti inflammatory effect and anti-cancer effect. Results : Compared to the control group, both the group medicated with Fructificatio Inonoti Obliqui total extract and with $50^{\circ}C$ low-temperature leachate were found to decrease the number of thrombocytes in blood plasma and NO content while to increase SOD activity and catalase activity significantly. Both groups also showed anti-inflammatory effect against THP-1 cells and a multiplication inhibition effect against liver cancer cells and stomach cancer cells significantly. Conclusions : Both Fructificatio Inonoti Obliqui total extract and Fructificatio Inonoti Obliqui $50^{\circ}C$ low-temperature leachate have significant antioxidant effect, anti inflammatory effect and anti cancer effect.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권8호
• /
• pp.4007-4011
• /
• 2012

Purpose: Retinoblastoma-interacting zinc finger gene (RIZ1) is a tumor suppressor gene which is highly inactivated by promoter hypermethylation in patients with liver fluke-related cholangiocarcinoma (CCA). Epigenetic aberration of this gene might withdraw the ability to restrain tumor cell proliferation and migration. We aimed to define the role of RIZ1 on cell proliferation and migration in CCA cell line. Materials and methods: Small interference RNA (siRNA) was used to knock down the expression of RIZ1 in a CCA-derived cell line in which cell proliferation and cell migration were performed. Results: A predominant nuclear localization of RIZ1 was observed. Reduction of RIZ1 by siRNA augmented cell proliferation and migration. Conclusion: The result suggested that RIZ1 might play a role in regulating cell proliferation and migration in CCA. Reduction of RIZ1 expression may aggravate the progression of CCA.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권5호
• /
• pp.1993-1995
• /
• 2015

Purpose: This analysis was conducted to evaluate the efficacy and safety of irinotecan based regimens as second-line chemotherapy in treating patients with small cell lung cancer. Methods: Clinical studies evaluating the efficacy and safety of irinotecan based regimens as second-line chemotherapy for patients with small cell lung cancer were identified using a predefined search strategy. Pooled response rates (RRs) of treatment were calculated. Results: In irinotecan based regimens as second-line chemotherapy, 4 clinical studies which including 155 patients with small cell lung cancer were considered eligible for inclusion. In all chemotherapy consisted of irinotecan with or without nedaplatin. Pooled analysis suggested that, in all patients, the pooled RR was 27.1% (42/155) in irinotecan based regimens. Nausea, vomiting, diarrhea and myelosuppression were the main side effects. No grade III or IV renal or liver toxicity was observed. No treatment related death occurred with the irinotecan based treatments. Conclusion: This systemic analysis suggests that irinotecan based regimens as second-line chemotherapy are associated with mild response rate and acceptable toxicity for patients with small cell lung cancer.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권8호
• /
• pp.3627-3630
• /
• 2012

The epithelial cell adhesion molecule (EpCAM) is a pan-epithelial differentiation antigen that is expressed on almost all carcinomas. However, a role in rat liver carcinogenesis has never been reported previously. Thus, its expression was investigated herein in rat liver tumors induced by diethylnitrosamine (DEN). Twenty male 5-week-old F344 rats were used in this experiment. Mini-osmotic pumps containing doses of 47.5 mg of DEN were inserted into the abdominal cavity of each animal to initiate liver carcinogenesis. All animals were sacrificed at 26 weeks after DEN treatment. At necropsy, hepatic masses were processed for histopathological examination, which revealed forty-four hepatocellular adenomas (HCAs) and twenty hepatocellular carcinomas (HCC). Tumors were immunohistochemically analyzed for EpCAM, proliferating cell nuclear antigen (PCNA) and co-localization of the two. EpCAM expression was mainly detected in hepatic tumor cells, showing a cytoplasmic staining pattern. However, expression was also slightly observed in normally-appearing surrounding hepatic cells. PCNA expression was highly detected in tumor cells, showing nuclear staining. Double staining of EpCAM and PCNA in tumors showed many cells with co-localization. Taken together, EpCAM and PCNA expression were increased in DEN-induced tumors and many tumor cells showed co-expression. It is suggested that EpCAM may increase during DEN-induced tumors, possibly associated with cell proliferation.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권18호
• /
• pp.7785-7792
• /
• 2014

Background: Valproic acid (VPA) is a potent anticancer and antiangiogenic agent. However, design and synthesis of chemical derivatives with improved antiangiogenic and anticancer activities are still necessary. In this study a library of novel derivatives of VPA was synthesized and tested. Methods: A human liver cancer cell line (HepG2) and a human normal embryonic kidney cell line (HEK 293) were exposed to various concentrations of VPA derivatives for 24 hours and cell viability was checked by MTT colorimetric assay. Anti-angiogenic properties were evaluated in transgenic zebrafish embryos. Results: N-valproylglycine derivatives suppressed survival almost 70% (p value 0.001) in HepG2 cells but only 10-12% in HEK 293 cells (p value 0.133). They also suppressed angiogenic blood vessel formation by 80% when used between $2-20{\mu}M$ in zebrafish embryos. Valproic acid hydrazides showed moderate level of anticancer activity by affecting 30-50% (p value 0.001) of cell viability in HepG2 cells and 8-10% in HEK293 cells (p value 0.034). Conclusion: The majority of compounds in this study showed potent and stronger antiangiogenic and anticancer activity than VPA. They proved selectively toxic to cancer cells and safer for normal cells. Moreover, these compounds inhibited developmental angiogenesis in zebrafish embryos. Based on the fact that liver is a highly vascularized organ, in case of liver carcinoma these compounds have the potential to target the pathological angiogenesis and could be an effective strategy to treat hepatocellular carcinoma.

• 약학회지
• /
• 제55권1호
• /
• pp.75-79
• /
• 2011

The replication competent adenoviral vector (AV), AdLPCDIRESE1A was generated and reported previously to have cytotoxic effects in some cell lines. In AdLPCDIRESE1A, the expression of cytosine deaminse (CD) and E1A genes are under the control of tumor-specific L-plastin promoter. CD enzyme can deaminate the nontoxic prodrug 5-fluorocytosine (5-FC) to the toxic 5-fluorouracil (5-FU). E1A gene is essential for viral replication. Primary liver cancer, most of which is hepatocellular carcinoma (HCC), is the third common leading cancer in Korea. Thus, we have conducted in vitro preclinical study to evaluate effectiveness of AdLPCDIRESE1A on HCC. The efficacy of cytotoxicity was measured by generation of cytopathic effect (CPE) and cell counting. We infected HepG2 cells with various MOI of vector alone or concurrent with 5-FC. Exposure of cells to AdLPCDIRESE1A generated a significant cytotoxic effect as compared to the control. Almost 83% of the cell had manifested the characteristic cytotoxic effect on day 9 after infection of cells with 10 MOI of vector. We also observed the additive cytotoxic effects when AdLPCDIRESE1A vector had been coadministrated with 5-FC. The results suggest that the use of AdLPCDIRESE1A/5FC may be value in treatment of liver cancer. Further animal studies are needed for clinical trial.

• BMB Reports
• /
• 제55권8호
• /
• pp.401-406
• /
• 2022

Ahnak, a large protein first identified as an inhibitor of TGF-β signaling in human neuroblastoma, was recently shown to promote TGF-β in some cancers. The TGF-β signaling pathway regulates cell growth, various biological functions, and cancer growth and metastasis. In this study, we used Ahnak knockout (KO) mice that underwent a 70% partial hepatectomy (PH) to investigate the function of Ahnak in TGF-β signaling during liver regeneration. At the indicated time points after PH, we analyzed the mRNA and protein expression of the TGF -β/Smad signaling pathway and cell cycle-related factors, evaluated the cell cycle through proliferating cell nuclear antigen (PCNA) immunostaining, analyzed the mitotic index by hematoxylin and eosin staining. We also measured the ratio of liver tissue weight to body weight. Activation of TGF-β signaling was confirmed by analyzing the levels of phospho-Smad 2 and 3 in the liver at the indicated time points after PH and was lower in Ahnak KO mice than in WT mice. The expression levels of cyclin B1, D1, and E1; proteins in the Rb/E2F transcriptional pathway, which regulates the cell cycle; and the numbers of PCNA-positive cells were increased in Ahnak KO mice and showed tendencies opposite that of TGF-β expression. During postoperative regeneration, the liver weight to body weight ratio tended to increase faster in Ahnak KO mice. However, 7 days after PH, both groups of mice showed similar rates of regeneration, following which their active regeneration stopped. Analysis of hepatocytes undergoing mitosis showed that there were more mitotic cells in Ahnak KO mice, consistent with the weight ratio. Our findings suggest that Ahnak enhances TGF-β signaling during postoperative liver regeneration, resulting in cell cycle disruption; this highlights a novel role of Ahnak in liver regeneration. These results provide new insight into liver regeneration and potential treatment targets for liver diseases that require surgical treatment.