• BMB Reports
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• 제56권10호
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• pp.557-562
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• 2023

Dysregulation of the E3 ubiquitin ligase Parkin has been linked to various human cancers, indicating that Parkin is a tumor suppressor protein. However, the mechanisms of action of Parkin remain unclear to date. Thus, we aimed to elucidate the mechanisms of action of Parkin as a tumor suppressor in human lung and colorectal cancer cells. Results showed that Parkin overexpression reduced the viability of A549 human lung cancer cells by inducing G2/M cell cycle arrest. In addition, Parkin caused DNA damage and ATM (Ataxia telangiectasia mutated) activation, which subsequently led to p53 activation. It also induced the p53-mediated upregulation of p21 and downregulation of cyclin B1. Moreover, Parkin suppressed the proliferation of HCT-15 human colorectal cancer cells by a mechanism similar to that in A549 lung cancer cells. Taken together, our results suggest that the tumor-suppressive effects of Parkin on lung and colorectal cancer cells are mediated by DNA damage/p53 activation/cyclin B1 reduction/cell cycle arrest.

• 한국동물학회지
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• 제12권1호
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• pp.22-28
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• 1969

Hiraizumi, Sandler, Crow(1960)는 미국의 Wisconsin 주 Madison의 D. melanogaster의 자연 집단을 분석하여 다수의 제 2 염색체가 SD 작용에 대한 억제 요인을 지니고 있음을 발견하였으며 최근에는 Hiraizumi 와 Nakajima(1965)가 일본의 자연 집단도 그러한 억제요인을 가지고 있다고 하였으며 Hiraizumi 와 Kataoka(1965)는 그 억제요인이 주로 X염색체에 있다고 보고 한바 있으며 Kataoka(1967)는 그 억제 요인의 X염색체상의 좌위를 결정하였고 억제요인을 지니고 있는 염색체의 빈도와 그 행동등 광범위한 연구를 한 바 있었다. 본인은 D. melanogaster의 한국 자연집단에도 이러한 억제요인이 SD 작용에 관여하고 있는지 (1)그리고 있으면 어떤 염색체에 들어 있는지 (2)를 연구하기 위하여 한국 9개 지역으로 부터의 자연집단 (춘천, 여수, 남해, 신촌, 광주(경기도), 군산, 광주, 제주, 부산)을 대상으로 하여 두가지 SD Stock[R-1, $R(SD^NH -1)-1$]을 사용하여 분석한 결과 다음 결론을 얻었다. 1. 9개 집단은 모두 억제 요인을 지니고 있었다. 2. 억제 요인은 대개 X염색체에 들어 있으며 그중 3 집단에서는 그 요인이 제 III 또는 IV 염색체에 그리고 제 II 염색체에 있는 경우도 있었다. 3. 기원이 다른 SD[R-1, 미국; $R(SD^NH -1)-1$, 일본]에 대한 억제 요인의 반응은 큰 차이를 볼 수 없었다.

• Journal of Gastric Cancer
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• 제14권3호
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• pp.147-155
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• 2014

Homeostatic imbalance between cell proliferation and death in gastric mucosal epithelia may lead to gastritis and gastric cancer. Despite abundant gastrokine 1 (GKN1) expression in the normal stomach, the loss of GKN1 expression is frequently detected in gastric mucosa infected with Helicobacter pylori, as well as in intestinal metaplasia and gastric cancer tissues, suggesting that GKN1 plays an important role in gastric mucosal defense, and the gene functions as a gastric tumor suppressor. In the stomach, GKN1 is involved in gastric mucosal inflammation by regulating cytokine production, the nuclear factor-${\kappa}B$ signaling pathway, and cyclooxygenase-2 expression. GKN1 also inhibits the carcinogenic potential of H. pylori protein CagA by binding to it, and up-regulates antioxidant enzymes. In addition, GKN1 reduces cell viability, proliferation, and colony formation by inhibiting cell cycle progression and epigenetic modification by down-regulating the expression levels of DNMT1 and EZH2, and DNMT1 activity, and inducing apoptosis through the death receptor-dependent pathway. Furthermore, GKN1 also inhibits gastric cancer cell invasion and metastasis via coordinated regulation of epithelial mesenchymal transition-related protein expression, reactive oxygen species production, and PI3K/Akt signaling pathway activation. Although the modes of action of GKN1 have not been clearly described, recent limited evidence suggests that GKN1 acts as a gastricspecific tumor suppressor. This review aims to discuss, comment, and summarize the recent progress in the understanding of the role of GKN1 in gastric cancer development and progression.

• 한국환경성돌연변이발암원학회지
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• 제25권3호
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• pp.118-123
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• 2005

Nicotine has been implicated as a potential factor in the pathogenesis of human lung cancer, however its mechanism of action in the development of lung cancer remains largely unknown. To explore the role of nicotine in the development of lung cancer, we first investigated the effects of nicotine on the expression of tumor associated genes by treating Sprague-Dawley rats with nicotine (10 mg/kg) by gavage once daily for 10 days. We determined the expression of proteins and mRNAs of the ras, raf, myc, jun, fos oncogenes and p53, Rb tumor suppressor genes by Western and Northern blotting, respectively. We did not detect any changes on the levels of proteins and mRNAs of these tumor associated genes in the lung of Sprague-Dawley rats from 3 days to 12 weeks after the last treatment of nicotine, indicating that nicotine appears to have no effect on expression of these oncogenes and tumor suppressor genes at an early stage in multistage chemical carcinogenesis. In a second experiment, we investigated the possibility that 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) could be formed endogenously by treating with nicotine and sodium nitrite. We treated groups of Fischer 344 rats with nicotine ($60{\mu}mol/kg$) and sodium nitrite ($180{\mu}mol/kg$), nicotine, sodium nitrite and NNK (120 nmol/kg) alone by gavage once daily for 7 days, respectively and determined the 8-hydroxydeoxyguanosine (8-OHdG), as an indicator of NNK formation, in the lungs of rats 24 hours and 48 hours after the last treatment by HPLC/ECD method. We detect increased level of 8-OHdG in the lungs of rats treated with NNK, but in the case of nicotine plus sodium nitrite, nicotine and sodium nitrite alone we could not detected any changes of 8-OHdG, respectively.

• 대한약침학회지
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• 제13권1호
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• pp.37-43
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• 2010

Objective : Ginseng is one of most widely used herbal medicine. Ginseng showed anti-metastasis activities. However, its molecular mechanisms of action are unknown. So we want to report the wild ginseng repress which plays key roles in neoplastic epithelial-mesenchymal transition process. Methods : Treatment of the human colorectal carcinoma LOVO cells and human gastric carcinoma SNU601 cells with the increased concentrations of cultivated wild ginseng extracts resulted in a gradual decrease in the AXIN2 gene expression. Results : Metastasis-suppressor genes, maspin and nm23 was not affected by the treatment of ginseng extracts in LOVO cells. Moreover, the mountain cultivated wild ginseng or mountain wild ginseng are similar in their inhibitory effects on the expression of AXIN2 gene, but are substantially stronger than cultivated ginseng. Conclusion : We described the novel mechanism of wild ginseng-induced anti-metastasis activity by repressing the expression of AXIN2 gene that plays key roles in epithelial-mesenchymal transition process.

• 약학회지
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• 제39권6호
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• pp.689-694
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• 1995

Sphingolipids play important roles in cell regulation and signal transduction. Recently, a sphinogomyelin cycle has been described in which activation of neutral sphingomyelinase leads to the breakdown of sphingomyelin and the generation of ceramide. Ceramide, in turn, has emerged as a candidate intracellular mediator for the action of certain cell agonists and has multiple biologic actions. Ceramide is a potent suppressor of cell growth and an inducer of apoptosis. The present studies show that exposure of IM-9 cells to ceramide resulted in internucleosomal cleavage of DNA, yielding laddered patterns of oligonucleosomal fragments characteristic of apoptosis. DNA fragmentation induced by ceramide was also confirmed by diphenylamine assay. The effect of ceramide on cell cycle progression was also studied. The addition of ceramide increase G$_{1}$ phase distribution in cell cycle. Cell cycle-related cyclin D$_{1}$ gene expression was decreased in a time-dependent manner. These results suggest that apoptosis induced by ceramide is related to cell cycle associated with the alteration of cell cycle in IM-9 cells.

• The Plant Pathology Journal
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• 제27권4호
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• pp.315-323
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• 2011

Soybean plants infected with Bean pod mottle virus (BPMV) develop acute symptoms that usually decrease in severity over time. In other plant-virus interactions, this type of symptom recovery has been associated with degradation of viral RNAs by RNA silencing, which is accompanied by the accumulation of virus-derived small interfering RNAs (siRNAs). In this study, changes in the accumulation of BPMV siRNAs were investigated in soybean plants infected with BPMV alone, or infected with both BPMV and Soybean mosaic virus (SMV) and in transgenic soybean plants expressing SMV helper component-protease (HC-Pro). In many potyviruses, HC-Pro is a potent suppressor of RNA silencing. In plants infected with BPMV alone, accumulation of siRNAs was positively correlated with symptom severity and accumulation of BPMV genomic RNAs. Plants infected with both BPMV and SMV and BPMV-infected transgenic soybean plants expressing SMV HC-Pro exhibited severe symptoms characteristic of BPMVSMV synergism, and showed enhanced accumulation of BPMV RNAs and siRNAs compared to plants infected with BPMV alone and nontransgenic plants. Likewise, SMV HC-Pro enhanced the accumulation of siRNAs produced from a silenced green fluorescent protein gene in transient expression assays, while the P19 silencing suppressor of Tomato bushy stunt virus did not. Consistent with the modes of action of HC-Pro in other systems, which have shown that HC-Pro suppresses RNA silencing by preventing the unwinding of duplex siRNAs and inhibiting siRNA methylation, these studies showed that SMV HC-Pro interfered with the activities of RNA-induced silencing complexes, but not the activities of Dicer-like enzymes in antiviral defenses.

• 동의생리병리학회지
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• 제17권3호
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• pp.819-825
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• 2003

pharbitis nil and Taraxacum mongolicum are representative herbs that have been used for cancer treatment in Korean traditional medicine. To understand the molecular basis of the antitumor function, we analyzed the effect of these herbs on proliferation and apoptosis of tumor cells using a gastric cancer cell line AGS. Cell counting assay showed that pharbitis nil strongly inhibit cell proliferation Of AGS whereas Taraxacum mongolicum exhibit no detectable effect on cellular growth. [³H]thymidine uptake analysis also demonstrated that DNA replication of AGS is suppressed in a dose-dependent manner by treatment with pharbitis nil. Additionally, tryphan blue exclusion assay showed that Pharbitis nil induce apoptotic cell death of AGS in a dose-dependent. To explore whether anti antiproliferative and/or proapototic property of Pharbitis nil is associated with their effect on gene expression, we performed RT-PCR analysis of cell cycle- and apoptosis-related genes. Interestingly, mRNA expression levels of c-Jun, c-Fos, c-Myc, and Cyclin D1 were markedly reduced by Pharbitis nil. Taraxacum mongolicum also showed inhibitory action on expression of these growth-promoting protooncogene but there effects are less significant, as compared to Pharbitis nil. Furthermore, it was also found that Pharbitis nil activates expression of the p53 tumor suppressor and its downstream effector p21Waf1, which induce G1 cell cycle arrest and apoptosis. Collectively, our data demonstrate that Pharbitis nil induce growth inhibition and apoptosis of human gastric cancer cells and these effects are accompanied with down-and up-regulation of growth-regulating protooncogenes and tumor suppressor genes, respectively. This observation thus suggests that the anticancer effect of Pharbitis nil might be associated with its regulatory capability of tumor-related gene expression.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7467-7471
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• 2014

SCY1-like 1-binding protein 1 (SCYL1BP1) is a newly identified transcriptional activator domain containing protein with many unknown biological functions. Recently emerging evidence has revealed that it is a novel regulator of the p53 pathway, which is very important for the development of human cancer. However, the effects of SCYL1BP1 on human lung squamous carcinoma cell biological behavior remain poorly understood. In this study, we present evidence that SCYL1BP1 can promote the degradation of MDM2 protein and further inhibit the G1/S transition of lung squamous carcinoma cell lines. Functional assays found that reintroduction of SCYL1BP1 into lung squamous carcinoma cell lines significantly inhibited cell proliferation, migration, invasion and tumor formation in nude mice, suggesting strong tumor suppressive function of SCYL1BP1 in lung squamous carcinoma. Taken together, our data suggest that the interaction of SCYL1BP1/MDM2 could accelerate MDM2 degradation, and may function as an important tumor suppressor in lung squamous carcinomas.

• 한국생물정보학회:학술대회논문집
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• 한국생물정보시스템생물학회 2001년도 제2회 생물정보학 국제심포지엄
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• pp.139-149
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• 2001

Since 1990, the National Cancer Institute(NCI) has screened more than 60.000 compounds against a panel of 60 human cancer cell lines. The 50-percent growth-inhibitory concentration (GI$_{50}$) values encode unexpectedly rich, detailed information on mechanisms of drug action and drug resistance. Each compound's pattern is like a fingerprint, essentially unique among the many billions of distinguishable possibilities. These activity patterns are being used in conjunction with molecular structural features of the tested agents to explore the NCI's database of more than 460, 000 compounds, and they are providing insight into potential target molecules and modulators of activity in the 60 cell lines. For example, the information is being used to search for candidate anticancer drugs that are not dependent on intact p53 suppressor gene function for their activity. It remains to be seen how effective this information-intensive strategy will be at generating new clinically active agents.s.