• 생약학회지
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• 제47권3호
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• pp.197-203
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• 2016

Decursin is a major component of the root of Angelica gigas(Umbelliferae), which has been traditionally used in Korea as a tonic and to treat anemia, hemiplegia, and women's diseases. The objective of this study is to identify the anti-cancer mechanism induced by decursin on apoptosis of human leukemia and lymphoma cells. Cytotoxicity of decursin on U937, HL-60, MOLT-4, THP-1 cells showed the significant effects. First of all, $IC_{50}$ of decursin on four cell lines was 27.1, 32.4, 17.4, $15.1{\mu}M$, respectively. So $IC_{50}$ in THP-1 cells was the smallest among 4 cell lines treated with decursin($15.1{\mu}M$). In order to understand the apoptosis-mechanism by decursin, we examined the gene expression of bcl-2(anti-apoptotic), bax(pro-apoptotic) and p53(tumor suppressor)after treating the THP-1 cells with decursin(10, 50 and $100{\mu}M$). It was found bcl-2 gene was decreased dose dependently, the expression level of bax gene of THP-1 cells treated with $100{\mu}M$ of decursin was about 3 times higher than those of control, and p53 gene was increased In the same concentration($100{\mu}M$), p53 gene was increased dose dependent manner. In protein express, bcl-2 and p53 protein showed a tendency to decrease. bax was increased about 4 fold. Therefore decursin is a useful chemotherapeutic agent against leukemia.

• Genomics & Informatics
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• 제3권3호
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• pp.74-79
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• 2005

The H19 gene, located at human chromosome 11p15.5, is imprinted in most normal human tissues. However, imprinting is often lost in tumors suggesting H19 is a putative tumor suppressor. We analyzed the single nucleotide polymorphisms (SNPs) of a 16 kb region that includes the H19 gene and its imprinting control region (ICR) in the Korean population. To identify SNPs, we directly sequenced this region in 18 Korean subjects. We identified 64 SNPs, of which 7 were in the exons of H19, 2 were in the introns, 14 were in the 3' intergenic region and 41 were in the 5' intergenic region. Of the 64 SNPs, 21 had not previously been reported and thus appear to be unique to the Korean population. The identified SNPs of H19 in the Korean population may eventually be useful as genetic markers associated with various diseases. In this study, 7 of the 64 identified SNPs were at CTCF binding sites in the ICR and may affect regulation of H19 gene imprinting. Thus, several genetic variations of the H19 gene may be important markers in human diseases that involve genomic imprinting, including cancer.

• Journal of Nutrition and Health
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• 제35권10호
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• pp.1053-1059
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• 2002

In post-genome period, the technique for identifying gene expression has been changed to high throughput screening. In the field of molecular nutrition, the need for this technique to clarify molecular function of the specific nutrient is essential. In this study, we have tested the zinc-regulated gene expression in zinc-deficient U937 cells, using cDNA microarray which is the cutting-edge technique to screen large numbers of gene expression simultaneously. The study result can be used for the preliminary gene screening data for clarifying, using monocyte U937 cell line, molecular Zn aspect in atherosclerosis. U937 cells were cultured in Zn-adequate (control, 12 $\mu$M Zn) or Zn-deficient (experimental, 0 $\mu$M Zn) ESMI media during 2 days, respectively. Cells were harvested and RNA was extracted. Total RNA was reverse-transcriptinized and synthesized cDNA probe labeled with Cy-3. fluorescent labeled cDNA probe was applied to microarray slide for hybridization slide, and after then, the slide was scanned using fluorescence scanner. ‘Highly expressed genes’ in Zn-deficient U937 cells, comparing to Zn-adequate group, are mainly about the genes for motility protein, immune system protein, oncogene and tumor suppressor and ‘Less highly expressed genes’ are about the genes for transcription, apoptosis associated protein, cell cycle, and several basic transcription factors. The results of this preliminary study imply the effectiveness of cDNA microarray for expression profiling of a singly nutrient deficiency, specially Zn. Furthur study, using tailored-cDNA array and capillary endothelial cell lines, would be beneficial to clarify molecular Zn function, more in detail.

• Journal of Chest Surgery
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• 제31권12호
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• pp.1200-1205
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• 1998

연구목적: 폐암은 protooncogene의 활성화와 종양억제유전인자(tumor suppressor gene)의 비활성화 등 다단 과정에 의하여 발생한다. 치료목적의 완전 절제가 가능하였던 제 IIIA기 비소세포폐암 환자에서 cyclin D1, p53, bcl-2 gene의 변이가 폐암에 미치는 영향을 조사하고자 하였다. 대상 및 방법: 1990년부터 1995년까지 연세의료원에서 치료목적의 완전절제가 가능하였던 stageIIIA 비소세포폐암 환자 100명의 paraffin block과 임상기록을 이용하였다. 각 환자의 조직절편을 labelled streptavidin-biotin method로 immunohistochemical 염색하였고 cyclin D1, p53, Bcl-2 immunostaining을 위한 조직절편들은 immunostaining하기 전 citrate buffer 내에서 10분에서 20분간 microwave oven으로 전처치한 후 cyclin D1은 NCL-cyclin D1-GM으로 p53는 lone DO-7으로 bcl-2는 clone 124로 overnight incubation하였다. 수술 후 평균 추적조사기간은 24.1 개월(range; 2∼84 개월)이었다. 결과: 100예의 폐암 중 56예가 편평상피세포암, 37예가 선암, 5예가 adenosquamous cell carcinoma, 2예가 대세포암이었고 수술 후 5년 생존율은 32.1%이었다. cyclin D1의 양성율은 35 %, p53는 56 %, bcl-2는 17 %였으나 cyclin D1, p53, Bcl-2 단백질 양성 발현과 생존율과의 상관관계는 없었다. 결론: 연구결과 cyclin D1, p53, Bcl-2 단백질 양성 발현이 비소세포폐암 발생기전과 연관되어 있으나 수술 후 예후인자로서는 부적당한 것으로 판단되었다.

• BMB Reports
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• 제30권3호
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• pp.205-210
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• 1997

p53 tumor suppressor plays an important role in the regulation of cellular proliferation. To identify proteins regulating the expression of p53 in rat liver, we analyzed p53 promoter by electrophoretic mobility shift assay (EMSA) and DNase I footprinting assay. We found that a protein binds the sequence CACGTG, bHLH consensus sequence in rat p53 promoter. Southwestern blotting analysis with oligonucleotides containing this sequence shows that the molecular weight of the protein is 100 kDa. This size is not compatible with the bHLH family such as USF or c-Myc/Max which is known to regulate the expression of the human and mouse p53 gene. Therefore this 100 kDa protein may be a new protein regulating basal transcription of rat p53. We purified this 100 kDa protein through sequence-specific DNA affinity chromatogaphy.

• 동의생리병리학회지
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• 제19권1호
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• pp.167-173
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• 2005

To investigate the possible molecular mechanism (s) of bee venom as a candidate of anti-cancer drug, we examined the effects of the compound on the growth of human lung carcinoma cell line A549. Bee venom treatment declined the cell growth and viability of A549 cells in a concentration-dependent manner, which was associated with induction of apoptotic cell death. Bee venom down-regulated the levels of anti-apoptotic genes such as Bcl-2 and Bcl-XS/L, however, the levels of Bax, a pro-apoptotic gene, were up-regulated. Bee venom treatment induced not only tumor suppressor p53 but also cyclin-dependent kinase inhibitor p21WAF1/CIP1 expression in a dose-dependent manner. Furthermore, bee venom treatment induced the down-regulation of telomerase reverse transcriptase mRNA and telomeric repeat binding factor expression of A549 cells, however, the levels of telomerase-associated protein-1 and c-myc were not affected. Taken together, these findings suggest that bee venom-induced inhibition of human lung cancer cell growth is associated with the induction of apoptotic cell death via regulation of several major growth regulatory gene products, and bee venom may have therapeutic potential in human lung cancer.

• Journal of Microbiology and Biotechnology
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• 제27권8호
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• pp.1367-1378
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• 2017

Epigenetic alterations such as DNA methylation, histone acetylation, and chromatin remodeling can control gene expression by regulating gene transcription. DNA methylation is one of the frequent epigenetic events that play important roles in cancer development. Cancer cells can gain significant resistance to anticancer drugs and escape programmed cell death through major epigenetic changes, including DNA methylation. To date, several research groups have identified instances of both (i) hypermethylation of tumor suppressor genes, and (ii) global hypomethylation of oncogenes. These changes in DNA methylation status could be used as biomarkers for the diagnosis and prognosis of cancer patients undergoing chemotherapies or other clinical therapies. Herein, we describe genes for which methylation is dependent upon anticancer drug resistance in patients with gastric cancer; we then suggest a significant epigenetic target to focus on for overcoming anticancer drug resistance.

• 대한골관절종양학회지
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• 제6권4호
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• pp.143-151
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• 2000

목적 : p53 종양억제 유전자는 사람의 암에서 변형이 가장 많이 발견되는 유전자로 유잉 육종에서 p53 유전자의 변형을 관찰하고자 하였다. 재료 및 방법 : 유잉육종 환자 35례의 파라핀 블록을 사용하였으며, 유전자의 결핍과 p53 유전자의 염기서열의 변형을 관찰하였다. 결과 : 정성적인 중합효소 연쇄반응을 이용한 p53의 4-9번까지의 유전자검사중 2례에서 동일성의 유전자 결핍이 관찰되었으며, exon 5-8의 유전자 중합효소 연쇄반응에서는 3례에서 missense 점돌연변이가 관찰되었다. 결론 : 이상의 결과로 p53은 유전적으로 적은 부분에서 유잉육종에 관여하는 것으로 관찰 되었다.

• BMB Reports
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• 제51권2호
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• pp.57-58
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• 2018

An accurate diagnostic marker for detecting early-stage hepatocellular carcinoma (eHCC) is clinically important, since early detection of HCC remarkably improves patient survival. From the integrative analysis of the transcriptome and clinicopathologic data of human multi-stage HCC tissues, we were able to identify barrier-to-autointegration factor 1 (BANF1), procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3 (PLOD3) and splicing factor 3b subunit 4 (SF3B4) as early HCC biomarkers which could be detected in precancerous lesions of HCC, with superior capabilities to diagnose eHCC compared to the currently popular HCC diagnostic biomarkers: GPC3, GS, and HSP70. We then showed that SF3B4 knockdown caused G1/S cell cycle arrest by recovering $p27^{kip1}$ and simultaneously suppressing cyclins, and CDKs in liver cancer cells. Notably, we demonstrated that aberrant SF3B4 overexpression altered the progress of splicing progress of the tumor suppressor gene, kruppel like factor 4 (KLF4), and resulted in non-functional skipped exon transcripts. This contributes to liver tumorigenesis via transcriptional inactivation of $p27^{kip1}$ and simultaneous activation of Slug genes. Our results suggest that SF3B4 indicates early-stage HCC in precancerous lesions, and also functions as an early-stage driver in the development of liver cancer.

• 대한의생명과학회지
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• 제18권4호
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• pp.413-419
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• 2012

The melanoma differentiation-associated gene-7 (MDA-7) protein, also known as interleukin-24 (IL-24), is a novel candidate of tumor suppressor that can induce apoptosis experimentally in a variety of human malignant cells. However, there have been few studies about its role in colorectal cancer. We performed immunohistochemical detection of MDA-7/IL-24 in 399 tissue samples from primary colorectal adenocarcinoma patients using a tissue microarray. Western blotting was then done to confirm the immunohistochemical observations. MDA-7/IL-24 immunoreactivity was observed in 116 (29.1%) of the 399 colorectal adenocarcinoma cases. Analysis of the MDA-7/IL-24 expression by Western blotting confirmed the immunohistochemical results. The tumors with a negative MDA-7/IL-24 expression more frequently showed poor differentiation (P=0004), lymph node metastasis (P=0.001), deep invasion (P=0.008) and high stage (P=0.001). A subset of colorectal adenocarcinoma revealed a decreased expression of MDA-7/IL-24, and this was associated with progressive pathologic features. These findings suggest that loss of MDA-7/IL-24 expression may play a role in tumor growth and progression of colorectal adenocarcinomas.