• 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.

• 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.

• 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.

• 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.

• Microbiology and Biotechnology Letters
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• v.24 no.1
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• pp.101-104
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• 1996

During the screening of inhibitor of DNA topoisomerase I from microbial secondary metabolites, Streptomyces melanosporofaciens 7489 which was capable of producing high level of inhibitor was selected from soil. The active compound (7489-1) was purified from the culture broth by solvent extraction, silica gel column chromatography and HPLC. The inhibitor was identified as dibutyl phthalate by spectroscopic methods of UV, $^{1}H$-NMR, $^{13}C$-NMR, DEPT and EI-MS. 7489-1 showed a strong inhibitory activity against topoisomerase I with 10 ${\mu}$M of $IC_{50}$ value.

• 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.

• YAKHAK HOEJI
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• v.49 no.5
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• pp.428-436
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• 2005

DNA topoisomerase I(TOP1) helps the control of DNA replication, transcription and recombination by assist­ing breaking and rejoining of DNA double strand. Camptothecin (CPT) and its derivative, topotecan, are known to inhibit TOP1 by intercalating into TOP1-DNA complex. Recently various non-CPT intercalators are synthesized for a new class of TOP1 inhibitors. In this study, six compounds isolated from Poria cocos were investigated for their interaction with TOP1­DNA complex using the flexible docking program, FlexiDock. The binding modes were analyzed and compared with the TOP1 inhibition activities. The compounds that showed potent activity were intercalated between the + 1/-1 base pairs of DNA, located near the active site phosphotyrosine723 and formed hydrogen bonds with active site residues. On the other hand, compounds with no activity were not docked at all. The binding modes were well correlated with the inhibition activity, suggesting the possibility that potent inhibitors can be designed from the information presented by the docking study.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.36 no.3
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• pp.177-185
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• 2010

Introduction: Epidermal growth factor receptor (EGFR) is expressed in human epithelial tumors including salivary cancers, and known to be correlated with tumor progression and poor clinical courses in some epithelial tumors. In this study, we determined the therapeutic effect of the anti-EGFR monoclonal antibody Erbitux (C225, cetuximab) in combination with the DNA topoisomerase I inhibitor irinotecan (CPT-11) on human salivary adenoid cystic carcinoma (SACC) cells growing in nude mice. Materials and Methods: At first, immunocytochemical analysis for the expression of EGFR and phosphorylated EGFR (pEGFR) on a human salivary ACC cell line (ACC3). To determine the in vivo effects of Erbitux and CPT-11, nude mice with orthotopic parotid tumors were randomized to receive intraperitoneal Erbitux (1 mg) two times per week, intraperitoneal Irinotecan (50 mg/kg) once per week, Erbitux plus CPT-11, or placebo. (control) Tumor volume and weight were measured. And mechanisms of in vivo activity of Erbitux and/or CPT-11 were determined by immunohistochemical/ immunofluorescent analyses. Results: Immunocytochemical staining of ACC3 demonstrated that EGFR was expressed and phosphorylated. CPT-11 inhibited ACC tumor growth in nude mice. Tumors of mice treated with CPT-11 and CPT-11 plus Erbitux exhibited increased tumor cell apoptosis and decreased microvessel density, which correlated with a decrease in the tumor volume in nude mice. But, CPT-11 seems not to be synergistic with Erbitux in our ACC3 model system. Conclusion: These results suggest that anti-EGFR monoclonal antibody and the DNA topoisomerase I inhibitor will be effective in the treatment of recurred or metastatic lesions of salivary ACC.

• Journal of Life Science
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• v.12 no.4
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• pp.469-476
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• 2002

The DNA topoismerase I inhibitor $\beta$-lapachone, the product of a tree from South America, is known to exhibit various biological properties, however the mechanisms of which are poorly understood. In the present report, we investigated the effects of $\beta$-lapachone on the growth of human prostate carcinoma DU-145 cells. Upon treatment with $\beta$-lapachone, a concentration-dependent inhibition of cell viability was observed and cells developed many of the hallmark features of apoptosis, including condensation of chromatin and DNA fragmentation. Flow cytometry analysis confirmed that $\beta$-lapachone increased populations of apoptotic-sub Gl phase. In addition, proteolytic cleavages of poly (ADP-ribose) polymerase (PARP) and $\beta$-catenin protein were observed after treatment of $\beta$-lapachone. These apoptotic effects of $\beta$-lapachone in DU-145 cells were associated with marked induction of Bax protein, however the levels of Bcl-2 expression were decreased in a dose-dependent manner.

• Archives of Pharmacal Research
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• v.23 no.4
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• pp.338-343
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• 2000

The effects of methanol extract of Rubus crategifolius roots and its solvent fractions were investigated on the proliferation of MCF-7 human breast carcinoma cells. The methanol extract inhibited the proliferation of MCF-7 cells in a concentration dependent manner. Moreover, their methanol soluble (W-M) fraction had the greatest inhibitory effect on the growth of MCF-7 cells. To evaluate whether the W-M fraction affects on the cell cycle of MCF-7 cells, cells treated with this fraction were analyzed with flow cytometry. The W-M fraction increased $G_0$/$G_1$phase after 24 h-treatment and induced apoptosis after 48 h-treatment. The hallmark of apoptosis, DNA fragmentation, also appeared by W-M fraction after 48 h-treatment. Furthermore, the methanol extract and its W-M fraction inhibited the activity of the topoisomerase 1 enzyme in the relaxation assay, From these results, their W-M fraction as well as methanol extract of R. crategifolius roots are necessary for further studies as a potent inhibitor of the growth of cancer cells.