• 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.

• BMB Reports
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• v.34 no.1
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• pp.85-89
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• 2001

Both topoisomerase $II{\alpha}$ and $II{\beta}$ east as phosphoproteins in the cells. Recently it was reported that DNA topoisomerase $II{\alpha}$ associates with and is phosphorylated by the extracellular signal-regulated kinase 2 (ERK2). Also, ERK2 stimulates the activity of topoisomerase II by a phosphorylation-independent manner [Shapiro et al., (1999) Mol. Cell. Biol. 19, 3551-3560]. In this study, a yeast two-hybrid system was used to investigate the binding site between topoisomerase $II{\alpha}$ or $II{\beta}$ and ERK2. The two-hybrid test clearly showed that topoisomerase $II{\beta}$ residues 1099-1263, and topoisomerase $II{\alpha}$ residues 1078-1182, mediate the interaction with ERK2, and that the leucine zipper motifs of topoisomerase $II{\alpha}$ and $II{\beta}$ are not required for its physical binding to ERK2. Our results suggest that topoisomerase $II{\beta}$ residues 1099-1263, and topoisomerase $II{\alpha}$ residues 1078-1182, may be common binding sites for activator proteins.

• YAKHAK HOEJI
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• v.40 no.6
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• pp.697-704
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• 1996

Quinolone derivatives, SJ5b (ethyl 5,12-dihydro-5-dihydro-5-oxobenzoxazolo[3,2-a]quinoline-6-carboxylate) and SQ7b (3-fluoro-2-(4-methylpiperazin-1-yl)-5.12-dihydro-5-oxobenzoxa zolo[3,2-a]quinoloine carboxylic acid) showed in vitro cytotoxicities against various tumor cell lines. SJ5b and SQ7b completely inhibited the DNA relaxation activities of human placental topoisomerase II at the concentration of 15.63 and 1.95 ${\mu}$g/ml, respectively. However, unlike etoposide which stabilize the topoisomerase II-DNA complex, SQ7b did not cause topoisomerase II-mediated DNA cleavage and SJ5b weakly stabilized the topoisomerase II-DNA cleavable complex. Through both experiments. DNA relaxation assay by the increment of topoisomerase II concentration and DNA unwinding assay, it was shown that SJ5b and SQ7b did not interact with topoisomerase II itself but bound to DNA. Therefore, it was concluded that DNA binding of SJ5b and SQ7b caused the inhibition of topoisomerase II related to DNA relaxation but no or very weak stabilization of topoisomerase II-DNA cleavable complex. In addition, SJ5b and SQ7b prevented whole cell nucleic acid syntheses in HL60 cells.

• 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.

• 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.

• 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.

• Korean Journal of Food Science and Technology
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• v.29 no.5
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• pp.1057-1062
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• 1997

In the course of searching for anticancer agents from 32 mushrooms, it was found that methanol extract of Lycoperdon perlatum showed inhibitory effect on topoisomerase II-mediated DNA cleavage. This active methanol extract was sequentially fractionated with hexane, chloroform, n-buthanol and water. Among the solvent-fractionated extracts, $1\;{\mu}g/mL$ hexane fraction of L. perlatum inhibited on topoisomerase II-mediated DNA cleavage. The effect of hexane fraction of L. perlatum was dose- and reaction time-dependent. The hexane fraction of L. perlatum was found to have inhibitory activity on relaxation assay of DNA topoisomerase I. The hexane fraction of cultured L. perlatum, however, had no inhibitory effect on either type of topoisomerase.

• 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.

• Journal of Microbiology and Biotechnology
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• v.6 no.5
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• pp.366-367
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• 1996

Dibutyl phthalate induced topoisomerase Ⅰ mediated DNA relaxation comparable to that of camptothecin, and topoisomerase Ⅱ mediated DNA relaxation equipotent to that of 4'-(9-acridinylamino) methanesulfon-m-anisidide (m-AMSA). The relaxation activities of dibutyl phthalate were dose-de-pendent and nearly as potent as those of camptothecin and m-AMSA.

• YAKHAK HOEJI
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• v.55 no.6
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• pp.441-445
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• 2011

A series of 8-(substituted)aryloxy- and 8-alkyloxy-caffenines were prepared from 8-bromocaffeine and (substituted) phenols as well as alkanols by Ullmann reaction and their inhibitory activities on topoisomerase II were evaluated. A compound, 8-(quinolin-2-yl)oxycaffeine showed the strongest inhibitory activity against topoisomerase II.