• Title/Summary/Keyword: Topoisomerase I

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Inhibition of DNA Topoisomerase I by Cryptotanshinone from Salvia miltiorrhiza

  • Lee, Dong-Sun;Hong, Soon-Duck
    • Journal of Microbiology and Biotechnology
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    • v.8 no.1
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    • pp.89-91
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    • 1998
  • Cryptotanshinone induced topoisomerase I-mediated DNA cleavage in vitro as strongly as camptothecin, whereas topoisomerase II-mediated DNA cleavage was not induced by this agent. In DNA relaxation assay using calf thymus DNA topoisomerase I and supercoiled pBR322 DNA, cryptotanshinone inhibited topoisomerase I-mediated DNA relaxation in a dose-dependent manner. In unwinding assay, cryptotanshinone ($50{\mu}M$) did not shift the topoisomers of DNA. These results suggest that cryptotanshinone exerted a preferential inhibition of topoisomerase I without intercalating into DNA.

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Topoisomerase I Inhibition of 2-Substituted 5-Nitrobenzimidazoles (2 위치가 치환된 5-니트로 Benzimidazole 유도체들의 Topoisomerase I 억제 활성)

  • ;Edmond J. LaVoie
    • YAKHAK HOEJI
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    • v.47 no.3
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    • pp.125-129
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    • 2003
  • A series of 2-phenyl-5-nitrobenzimidazoles substituted at the para positon of the 2-phenyl moiety was synthesized & evaluated for their activity to inhibit topoisomerase I. The structure-activity relationship study revealed that neither the electronic nor lipophilic parameters were related to the topoisomerase I inhibition. A strict spatial requirement seems to be present for retention of topoisomerase I inhibition activity.

Inhibition of DNA Topoisomerase I by Cyclo(L-Prolyl-L-Phenylalanyl) Isolated from Streptomyces sp. AMLK-335

  • Rhee, Ki-Hyeong
    • Journal of Microbiology and Biotechnology
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    • v.12 no.6
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    • pp.1013-1016
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    • 2002
  • Cyclo(L-prolyl-L-phenylalanyl) [cyclo(pro-phe)] was isolated from Streptomyces sp. AMLK-335 and found to inhibit DNA topoisomerase I activity. In a DNA relaxation assay using supercoiled pBR322 DNA, cyclo(pro-phe) inhibited the DNA topoisomerase activity more strongly than camptothecin, a known topoisomerase inhibitor. However, at a concentration of $10{\mu}M$, cyclo(pro-phe) produced a lower degree of DNA relaxation than camptothecin, therefore, the inhibition of topoisomerase I activity by cyclo(pro-phe) was also found to be dose dependent. Accordingly, the current results suggest that cyclo(pro-phe) may be a novel inhibitor of topoisomerase I.

Parameter Focusing on the Topoisomerase I-inhibition Activities of 1-(2-furyl)-3-phenylpropenone Derivatives (1-(2-furyl)-3-phenylpropenone 유도체의 DNA Topoisomerase I 저해활성에 대한 parameter focusing)

  • 명평근;최수라;성낙도
    • YAKHAK HOEJI
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    • v.44 no.4
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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.

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Effects of Inhibitors on the Function and Activity of Topoisomerase, and Gene Expression in HL-60 Human Leukemia Cells (HL-60 세포의 유전자 발현 및 topoisomerase의 기능 활성에 미치는 억제제의 영향)

  • Jeong, In-Cheol;Cho, Moo-Youn;Park, Jang-Su
    • Journal of Life Science
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    • v.18 no.1
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    • pp.75-83
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    • 2008
  • This studies were designed to elucidate whether inhibitors of topoisomerase regulate function and activity of topoisomerase, and gene expression in HL-60 human leukemia cells. HL-60 cells were treated with 10-hydroxycamptothecin or doxorubicin, total RNA was isolated, and expressed genes were investigated with human oligonucleotide microarray containing 10K gene, respectively. Expression profiles of the human leukemia HL-60 cells treated with 10-hydroxycamptothecin (10-CIT) or doxorubicin associated with signal transduction,. cell adhesion, cell cycle, cell growth, cell proliferation, cell differentiation, transcription and immune response, especially genes related with transcription and cell growth. In HL-60 cells treated with 10-CPT, the expression of topoisomerase III${\alpha}$, III${\beta}$ and I gene from oligo chip microarray analysis were increased over, but the expression of topoisomerase II${\alpha}$ and II${\beta}$ gene were decreased over. In contrast, the expression of topoisomerase II${\alpha}$ and II${\beta}$ gene were increased over in HL-60 cells treated with doxorubicin, whereas the expression of topoisomerase III${\alpha}$ and III${\beta}$ mRNA remained no significant change. These results suggest that these data may be useful for novel therapeutic markers.

Anticancer Activity of Indeno[1,2-b]-Pyridinol Derivative as a New DNA Minor Groove Binding Catalytic Inhibitor of Topoisomerase IIα

  • Jeon, Kyung-Hwa;Shrestha, Aarajana;Jang, Hae Jin;Kim, Jeong-Ahn;Sheen, Naeun;Seo, Minjung;Lee, Eung-Seok;Kwon, Youngjoo
    • Biomolecules & Therapeutics
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    • v.29 no.5
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    • pp.562-570
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    • 2021
  • Topoisomerase IIα has been a representative anti-cancer target for decades thanks to its functional necessity in highly proliferative cancer cells. As type of topoisomerase IIα targeting drugs, topoisomerase II poisons are frequently in clinical usage. However, topoisomerase II poisons result in crucial consequences resulted from mechanistically induced DNA toxicity. For this reason, it is needed to develop catalytic inhibitors of topoisomerase IIα through the alternative mechanism of enzymatic regulation. As a catalytic inhibitor of topoisomerase IIα, AK-I-191 was previously reported for its enzyme inhibitory activity. In this study, we clarified the mechanism of AK-I-191 and conducted various types of spectroscopic and biological evaluations for deeper understanding of its mechanism of action. Conclusively, AK-I-191 represented potent topoisomerase IIα inhibitory activity through binding to minor groove of DNA double helix and showed synergistic effects with tamoxifen in antiproliferative activity.

Antimutagenic and DNA Topoisomerase I Inhibition Effects of Sarcodon aspratus Extracts (향버섯(Sarcodon aspratus)추출물의 항돌연변이성 및 DNA Topoisomerase I 저해 효과)

  • 배준태;이갑랑
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.29 no.5
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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.

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Numerical Identification of an Actinomycetes Strain Producing an Antitumor Antibiotic with Inhibitory Activity against DNA Topoisomerase (DNA topoisomerase I Inhibitor 를 생성하는 방선균 분리균주의 수리동정)

  • Lee, Dong-Sun;Ha, Sang-Chul;Shin, Woo-Chang;Kim, Tae-Ho;Kim, Hong-Joong;Park, Yong-Ha;Kim, Jong-Guk;Hong, Soon-Duck
    • Microbiology and Biotechnology Letters
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    • v.23 no.2
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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.

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Falcarindiol, a Polyacetylenic Compound Isolated from Peucedanum japonicum, Inhibits Mammalian DNA Topoisomerase I

  • Lee, Gwang;Park, Hyoung-Gun;Choi, Mi-Lim;Kim, Young-Ho;Park, Yong-Bok;Song, Kyung-Sik;Cheong, Chaejoon;Bae, Young-Seuk
    • Journal of Microbiology and Biotechnology
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    • v.10 no.3
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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.

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