• 생약학회지
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• 제30권1호
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• pp.1-6
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• 1999

To evaluate cytotoxic effect and topoisomerase I inhibition activity of Caesalpinia sappan L., both water and methanol extracts were examined using in vitro assay. The cytotoxic effect of Caesalpinia sappan L. examined using MTT and SRB assay and $IC_{50}$ values were measured against U937, HL60, HepG2, SNU-1, SNU-16 cancer cell lines. Among them the representative cytotoxic results are shown as follows; water extract (U937=13.39 ${\mu}g/ml$, HL60=8.65 ${\mu}g/ml$, HepG2=38.48 ${\mu}g/ml$, SNU-1=7.72 ${\mu}g/ml$, SNU-16=25.49 ${\mu}g/ml$), methanol extract (U937=13.35 ${\mu}g/ml$, HL60=9.43 ${\mu}g/ml$, HepG2=25.67 ${\mu}g/ml$, SNU-1=8.37 ${\mu}g/ml$, SNU-16=28.64 ${\mu}g/ml$). The inhibitory concentration of DNA topoisomerase I activity against water extract was 100 ${\mu}g/ml$ and the inhibitory concentration of DNA topoisomerase I against methanol extract was 400 ${\mu}g/ml$.

• 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.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.314.2-314.2
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• 2002

DNA topoisomerases catalyze changes in DNA topology through cycles of transient DNA strand breakage and religation. During this process. the active site tyrosine in human DNA topoisomerase Ⅰ(Top Ⅰ) becomes covalently linked to the 3'-ends of a single-stranded nick in the DNA duplex, Stabilization of the Top Ⅰ-DNA cleavable complex is the common initial event leading to the cytotoxicity of top 1 inhibitors. (omitted)

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.159.1-159.1
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• 2003

Human Topoisomerase I (topo I) helps the control of DNA supercoiling in cells by assisting breaking and religation of DNA strand. It is essential for cellular metabolism and survival, hence, a good target for a novel class of anticancer drugs. As topo I inhibitor binds to the DNA-topo I complex, the religation of DNA strand is suppressed which results in the death of the target cell. Seven compounds of H-Imidazo［4, 5-g］phthalazing-4, 9-dione derivatives with $IC_50$ in the range of 0.001 and 6.27 $\mu$M in 5 different cancer cells and four compounds of 7-chloro-6-quinazoline-5, 8-dione derivatives with positive and negative topo I inhibition activities were studied. (omitted)

• Bulletin of the Korean Chemical Society
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• 제26권11호
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• pp.1829-1832
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• 2005

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.180.1-180.1
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• 2003

Eukaryotic DNA topoisomerase I (top I) is an essential enzyme that act to relax supercoiled DNA during the transcription, replication and mitosis. Intracellular levels of top I are elevated in a number of human solid tumors, relative to the respective normal tissues, suggesting that controlling the topI level is important to treat cancer. Top I poisons show their antitumor activities by stabilizing the cleavable ternary complex consisting of top I enzyme, DNA, and drug. Thus, top I is a promising target for the development of new cancer chemotherapeutics against a number of solid tumors. (omitted)

• 대한화학회지
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• 제49권5호
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• pp.449-460
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• 2005

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.315.1-315.1
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• 2002

DNA topoisomerases I (topo I) and II are essential enzymes that relax DNA supercoiling and relieve torsional strain during DNA processing. including replication. transcription. and repair. Topo I relaxes DNA by cleaving one strand of DNA by attacking a backbone phosphale with a catalytic lyrosine (Tyr723. human topo I). This enzyme has recently been investigated as a new target for antineoplastic drugs. Inhibitors to the enzyme intercalate between the DNA base pairs. interfering religation of cleaved DNA, therefore inhibit the activity of topo I. (omitted)

• Natural Product Sciences
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• 제17권3호
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• pp.245-249
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• 2011

Eight compounds, squalene (1), friedelin (2), ${\beta}$-sitosterol (3), ${\beta}$-sitosterol-3-O-glucoside (4), ${\alpha}$-tocopherol (5), betulinic acid (6), trilinolein (7) and 1-O-(9Z,12Z-Octadecadienoyl)-3-nonadecanoyl glycerol (8), were isolated from the barks of Tilia amurensis. Their chemical structures were identified by comparing their physicochemical and spectral data with those published in the literature. These isolated compounds were examined for their inhibitory activities against topoisomerase I and II. Compound 7 showed significant inhibition of DNA topoisomerase I and II activities, with percent decreases in activity of 87 and 95%, respectively at a concentration of $100\;{\mu}M$. Compound 6 exhibited cytotoxicity against the human colon adenocarcinoma cell line (HT-29), the human breast adenocarcinoma cell line (MCF-7) and the human liver hepatoblastoma cell line (HepG-2), with $IC_{50}$ values of 20, 59 and $16\;{\mu}M$, respectively.

• 생명과학회지
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• 제12권4호
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• pp.469-476
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• 2002

남미지역에 서식하는 Tabebuia avellanedae의 수피에서 동정된 천연 quinone계 물질인 $\beta$-lapachone은 DNA topoisomerase I 억제제 이외 다양한 약리학적 기능이 있을 것으로 추정되지만 그 기능이 명확하지 않다. $\beta$-lapachone의 생리활성 기전 해석의 일환으로 본 연구에서는 인체 전립선 DU-145 암세포주의 성장에 미치는 $\beta$-lapachone의 영향을 조사하였다. p-lapachone이 함유된 배지에서 자란 암세포들은 $\beta$-lapachone 처리 농도 의존적으로 성장이 억제되었으며, 이는 apoptosis가 유발된 세포에서 특징적으로 관찰되는 chromatin condensation 및 DNA fragmentation 현상을 유발하였고, DNA flow cytometry 분석결과 apoptotic-sub Gl기에 해당하는 세포들의 빈도도 증가되었다. 또한 poly (ADP-ribose) polymerase 및 $\beta$-catenin 단백질의 발현에서도 apoptosis 유발 특이적인 분해 현상을 보여주었으며, DU-145 전립선 암세포에서 $\beta$-lapachone에 의한 이러한 apoptosis의 유발에는 Bax의 발현증가에 따른 Bcl-2 발현의 감소가 중요한 역할을 할 고 있는 것으로 사료된다.