• 한국동물학회지
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• 제36권3호
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• pp.367-372
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• 1993

재생쥐간에서 분리한 topoisomerase II에서 protein kinase 활성이 발견되었다. ,topo II 활성 및 kinase 활성은 hydroxyapatite, phosphocellulose, double strand DNA cellulose chromatography 등의 순수 분리 과정 중에도 서로 분리되지 않았으며 glycerol gradient sedimentation 분석에서도 같은 분획에서 활성이 존재하였다. Kinase는 topo II 저해제인 N-ethylmaleimide와 novobiocin 등에 의해 그 활성이 저해되었다. 그러나 이러한 증거들 만으로 kinase 활성이 topo II가 아닌 다른 polypeptide에 의한 것일 가능성을 완전히 배제 할 수는 없다. Topo II와 결합된 kinase 활성에는 Mg++가 절대적으로 필요하였으며 다른 일가 또는 이가 이온으로는 그 효과가 대체되지 않았다. Histone H1은 kinase 활성을 증가 시키며 또 kinase에 의해 강하게 인산화된다. 이러한 효과는 다른 histone 류 및 casein 등에 의해 대체되지 않았다.

• 약학회지
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• 제44권4호
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• pp.358-361
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• 2000

Parameter focusing on the DNA topoisomerase-Iinhibition with X-substituted phenyl substituents in 1-(2-furyl)-3-phenylpropenone derivatives as inhibition material were analyzed. From the basis on the results the inhibition on DNA topoisomerase I suggested that the inhibition activities of X-substituted phenyl substitutents would depend largely on the net charge of $\beta$-carbon atom, LUMO energy (e.v.) and STERIMOL parameter B$_{5}$ (width) of X. Among them, non-substituent (X=H), 1 and 2,2-dichloro substituent, 4 showed the highest DNA topoisomerase-I inhibition activity.y.

• Archives of Pharmacal Research
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• 제27권1호
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• pp.77-82
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• 2004

DA-125, a novel derivative of adriamycin, is known for its anti-cancer activity. In this study, the inhibitory mechanism of DA-125 on topoisomerase was investigated in the simian virus 40 (SV40) replicating CV-1 cell by studying the SV40 DNA replication intermediates and DNA-topoisomerase complexes. DNA-protein complexes that were formed in the drug-treated cells were quantitated by using a glass filter assay. SV40 DNA replication intermediates that were accumulated in the drug-treated CV-1 cell were analyzed in a high resolution gel. DA-125 did not accumulate B-dimers of SV40 DNA replication intermediates which were found in the adriamycin-treated CV-1 cells. DA-125 induced a dose-dependent formation of the DNA-protein complexes, while adriamycin did not. When adriamycin and etoposide (VP16) were added to the SV40-infected cells at the same time, adriamycin blocked the formation of the DNA-protein complexes induced by VP16 in a dose-dependent manner. However, DA-125 blocked the formation of the DNA-protein complexes induced by VP16 up to the maximum level of the DNA-protein complexes that were induced by DA-125 alone. Adriamycin and DA-125 did not inhibit the formation of the DNA-protein complexes that were caused by camptothecin, a known topoisomerase I poison. DA-125 is bifunctional in inhibiting topoisomerase II because it simultaneously has the properties of the topoisomerase II poison and the DNA intercalator. As a topoisomerase II poison, DA-125 alone induced dose-dependent formation of the DNA-protein complexes. However, as a DNA intercalator, it quantitatively inhibited the formation of the DNA-protein complexes induced by a strong topoisomerase II poison VP16. Furthermore considering that the levels of the DNA-protein complex induced by VP16 were decreased by DA-125 in terms of the topoisomerase II poison, we suggest that DA-125 has a higher affinity to the drug-binding sites of DNA than VP16 has.

• 한국미생물·생명공학회지
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• 제23권2호
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• pp.123-130
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• 1995

DNA topoisomerase I have been shown to be important therapeutic target in cancer chemotherapy. Chemotaxonomy and numerical identification were carried out for an isolate strain No.7489 producing an antibiotic that inhibits DNA topoisomerase I activity. The genus of strain No.7489 was determined as Streptomyces sp. from culture, morphological and chemotaxonomic data. Thirty-nine taxonomic unit characters were tested and the data were analyzed numerically using the TAXON program. The isolate was best matched to Streptomyces melanosporofaciens in the major cluster 32 of Streptomyces. Therefore, it was concluded that the isolate was identified to be a member of Streptomyces melanosporofaciens.

• 약학회지
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• 제43권5호
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• pp.623-628
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• 1999

DA-125, a new antitumor agent, was compared with adriamycin, a known DNA intercalator, in terms of inhibitory mechanism of DNA replication by using replicating simian virus 40 (SV40) genome in vivo. In analyzing the SV40 DNA replication intermediates present in cells treated with DA-125, it was not observed to accumulate B-dimers of SV40 DNA which are prominent in adriamycin-treated cells. However, treatment with DA-125 induced dose-dependent formation of DNA-topoisomerase complex which is characteristic of topoisomerase poisons. In addition, DA-125 showed more efficient in inhibiting SV40 DNA replication than adriamycin. Therefore, on the basis of this observation, we suggest that DA-125, a derivative of adriamycin, inhibits DNA replication by blocking topoisomerase activity as a toposomerase poison although adriamycin blocks topoisomerase activity as a DNA intercalator.

• 한국식품영양과학회지
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• 제29권5호
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• pp.917-921
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• 2000

This study was carried out to investigate the effects on the mutagenicity and activity of DNA topoisomerase I of Sarcodon aspratus. Using an Ames mutagenicity test, which has been used to assess both mutagenic and antimutagenic effects of various molecules, it was observed that the methanol extracted fraction and other fractions (prepared in water or ethylacetate) of Sarcodon aspratus showed a significant antimutagenic activity against a mutagenecity induced by both a direct mutagenic agent such as MNNG and an indirect mutagenic agents such as B(a)P and AFB$_1$in Salmonella typhimurium TA98, TA100. Also, the extract and fractions of Sarcodon aspratus were found to have an inhibitory activity on the relaxation process of DNA topoisomerase I.

• Journal of Microbiology and Biotechnology
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• 제10권3호
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• pp.394-398
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• 2000

A methanol extract of the root of Peucedanum japonicum, used as a medicinal herb, showed an inhibitory effect on mammalian topoisomerase I activity. The methanol extract was suspended in ethyl acetate, and a topoisomerase I inhibitor in the organic soluble fraction was then isolated by silica gel and thin layer chromatography. The topoisomerase I inhibitory compound was indentified as falcarindiol based on the analysis of EI-MS, $^1$H and \ulcornerC NMR spectroscopy. This inhibitory showed cytotoxicity against human leukemia Jurkat T and HL60 cells with an IC\ulcorner value of 7 $\mu\textrm{g}$/ml. These results suggest the possibility of falcarindiol as a new anticancer agent which can be expected to have a synergistic effect on other anticancer drugs. In addition, the present data show that falcarindiol has antifungal, yet not antibacterial, activity.

• Animal cells and systems
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• 제6권3호
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• pp.277-282
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• 2002

Topoisomearse II is an essential enzyme in all organisms with several independent roles in DNA metabolism. Recently, it has been demonstrated that the C-terminal region of topoisomerases II is associated with hetero-logous protein-protein interactions in human and yeast. In this study, we identified that RTP1, a rat homologue of EIA binding protein BS69, is another topoisomerae II interacting protein by yeast two-hybrid screening. RTP1 has an E1A-binding domain and a MYND motif, which are known to be required for transcriptional regulation by binding to other proteins and interaction with the leucine zipper motif of topoisomerase II. The physical interaction between RTP1 and topoisomerase ll$\alpha$ was examined by GST pull-down assay in vitro. The expression level of RTP1 peaks in S phase as that of topoisomerase ll$\alpha$. These results suggest that the interaction between topoisomerase ll$\alpha$ and RTP1 might play an important role in regulating the transcription of genes involved in DNA metabolism in higher eukaryotes.

• Journal of Microbiology and Biotechnology
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• 제29권4호
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• pp.571-576
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• 2019

Microenvironmental stress, which is naturally observed in solid tumors, has been implicated in anticancer drug resistance. This tumor-specific stress causes the degradation of topoisomerase $II{\alpha}$, rendering cells resistant to topoisomerase $II{\alpha}$-targeted anticancer agents. In addition, microenvironmental stress can induce the overexpression of 78kDa glucose regulated protein (GRP78), which can subsequently block the activation of apoptosis induced by treatment with anticancer agents. Therefore, inhibition of topoisomerase $II{\alpha}$ degradation and reduction in GRP78 expression may be effective strategies for inhibiting anticancer drug resistance. In this study, we investigated the active compound arctigenin, which inhibited microenvironmental stress-induced etoposide resistance in HT-29 cells. Arctigenin was also highly toxic to etoposide-resistant HT-29 cells, with an $IC_{50}$ value of $10{\mu}M$ for colony formation. We further showed that arctigenin inhibited the degradation of topoisomerase $II{\alpha}$ and reduced the expression of GRP78. Thus, these results suggest that arctigenin is a novel therapeutic agent that inhibits resistance to etoposide associated with microenvironmental stress conditions.

• Applied Biological Chemistry
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• 제43권3호
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• pp.228-230
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• 2000