• Title/Summary/Keyword: Intercalating agent

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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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Synthesis and Cytotoxicity of 4-Carbamoyloxymethyl-1-azaanthraquinones (4-카바모일옥시메틸-1-아자안트라퀴논 유도체들의 합성 및 세포독성)

  • Lee, Hee-Soon;Lee, Seung-Il;Hong, Seoung-Soo;Cho, Jung-Sook;Kim, Young-Ho
    • YAKHAK HOEJI
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    • v.42 no.5
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    • pp.507-512
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    • 1998
  • In the course of developing novel antitumor intercalating agents. We synthesized 4-carbamoyloxymethyl-l-azaanthraquinones 7-12, incorporating the latent alkylating functi onality. These compounds were designed to explore the effect of substituent on the nitrogen of carbamate. The target compounds were prepared by hetero Diels-Alder reaction as a key step followed by functionalization of benzylic methyl to the desired substituents. Growth inhibitory studies of the azaanthraquinones were conducted in vitro against human cancer cell lines (SNU-354; liver and MCF7; breast) and human epidermoid carcinoma cells that are sensitive (KB-3-1) and multidrug-resistant (KB-V-1). The compounds were less potent than doxorubicin against sensitive cell lines. However, the most active compound 12 was not cross-resistant with doxorubicin against KB-V-1.

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Synthesis and Cytotoxicity of 3-Carbamoyloxymethyl-1-azaanthraquinones (3-카바모일옥시메틸-1-아자안트라퀴논 유도체들의 합성 및 세포독성)

  • Lee, Hee-Soon;Choi, Jae-Young;Hong, Seoung-Soo;Cho, Jung-Sook;Kim, Young-Ho
    • YAKHAK HOEJI
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    • v.41 no.6
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    • pp.718-723
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    • 1997
  • In the course of developing novel antitumor intercalating agents, we synthesized 3- carbamoyloxymethyl-azaanthraquinones 6-12, incorporating the latent alkylating functionality. These compounds were designed to explore the effect of heteroatom incorporation into anthraquinone chromophore and the effect of the incorporation of the latent alkylating functionality. The derivatives were prepared by hetero Diels-Alder reaction as a key step followed by functionality of allylic methyl to the desired substituents. Growth inhibitory studies of the azaanthraquinones were conducted in vitro against human cancer cell lines (SNU-354: liver and MCF7: breast) and human epidermoid carcinoma cells that are sensitive (KB-3-1) and multidrug-resistant (KB-V-1). The derivatives were 10 to 100-fold less potent than doxorubicin against sensitive cell lines. However, they were marginally cross-resistant with doxorubicin against KB-V-1.

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Toxic Activities of the Oxidant Chromate in Culture Cells (산화성 크롬의 배양세포에서의 독성작용)

  • 박형숙
    • Environmental Analysis Health and Toxicology
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    • v.13 no.1_2
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    • pp.1-9
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    • 1998
  • The ROS-producing potency of chromium compounds of several oxidation states were determined in the H4 cells. $K_2Cr_2O_7$ as Cr (VI), synthetic Cr (V) compounds and Cr (III) as TPP produced high level of ROS. However, ROS values of Cr-picolinate as Cr (III), CrCl$_2$, CrCI$_2$, were almost equal to the control. The effects of physiological antioxidants compounds which react with free radicals were examined for their effects on chromate-induced production of reactive oxygen species (ROS) in A549 cells after the addition of $K_2Cr_2O_7$. The compounds used were vitamin C (ascorbate), vitamin E ($\alpha$-tocopherol), superoxide dismutase (SOD) and catalase. The preincubation of ascorbate (200uM) with A549 cells for 20hr resulted in a significant reduction of hexavalent chromate(100uM) induced ROS. However, there is no effects of preincubation of the cells with vitamin E succinate (10 and 20uM, 20hr) on the ROS production. Also, the effects of Cr (VI) on the cell cycle of A549 cells was measured by adding the DNA intercalating agent, propidium iodide. S phase of the cell cycle was increased by the chromium (VI) compounds up to 20uM indicating toxicity or possible mitogenic action of the cell. The shoulder in Go/G1 phase at 20uM Cr (VI) with 24 hr treatment indicates apoptosis.

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DNA Bis-intercalating Agent, Echinomycin-induced Apoptosis via Bcl-2 Dependence Pathway in Human Colon Cancer Cells

  • Park, Ju-Youn;Ryang, Yong-Suk;Kim, Jong-Bae;Chang, Jae-Ho;Cho, Hyeon-Cheol;Kim, Soo-Ki
    • Molecular & Cellular Toxicology
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    • v.4 no.2
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    • pp.144-149
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    • 2008
  • Despite versatile activity (cancericidal, antimicrobial, hypoxia inducible factor (HIF) inhibition, immune deactivation of DNA bis-intercalation agent, echinomycin, its specific mechanism has been elusive. Of these novel mechanisms, we reported that using human colon cancer cells (HT-29), apoptotic machinery induced by echinomycin might be dependent of caspase-3 pathway. Despite a partial enlightenment of prototypic signal path triggered by echinomycin, the role of Bcl-2 in this signaling pathway is unclear. To address this issue, we explored whether or not echinomycin would overcome the anti-apoptotic impact of Bcl-2 in HT-29 cells by the controlled Bcl-2 overexpression. Prior to this proof, we confirmed that echinomycin induces mitochondrial depolarization, then triggering the mitochondrial pathway of apoptosis with an involvement of upstream cas-pases-3. Transiently transfection with inactive Bax-DNA failed to prevent echinomycin-induced apoptosis in HT-29 cells. To dissect the role of Bcl-2 in echinomycin-induced apoptosis, HT-29 cells were transiently transfected with Bcl-2 DNA for overexpression and then treated with echinomycin for 24h. Combined analyses of DNA fragmentation and flow cytometric analysis clearly verified that echinomycin-induced apoptosis was drastically attenuated by Bcl-2 overexpression, whereas a control vector rarely affected echinomycin-induced apoptosis. Collectively, these data verify that Bcl-2 regulates echinomycin-induced apoptosis in HT-29 cells. To my knowledge, this is the first evidence that of diverse, structured minor groove binders (MGB), the prototypic echinomycin might control the apoptotic signaling via Bcl-2-mitochondrial pathway.

Ethidium monoazide-PCR for the detection of viable Escherichia coli in aquatic environments (수환경에서 살아 있는 대장균의 검출을 위한 ethidium monoazide-중합효소연쇄반응법)

  • Lee, Gyucheol;Kim, Hyunjeong;Lee, Byunggi;Kwon, Soonbok;Kim, Gidon;Lee, Sangtae;Lee, Chanhee
    • Journal of Korean Society of Water and Wastewater
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    • v.23 no.2
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    • pp.199-205
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    • 2009
  • It is very important to differentiate of DNA derived from live or dead bacteria within mixed microbial communities in aquatic environments. Ethidium monoazide (EMA) is a DNA intercalating agent and the treatment of EMA with strong visible light cleaves the genomic DNA of bacteria. In dead bacterial cells, EMA intercalates into the genomic DNA, induces the cleavage of DNA, and inhibits the PCR amplification. In this study, we developed the EMA-PCR and EMA real-time PCR to detect the DNA derived from viable Escherichia coli (E.coli) in mixed cultures of live and dead E.coli. The treatment of EMA, $50{\mu}g/mL$, and 650 W visible halogen light exposure for 2 minutes cleaved the genomic DNA derived from heat killed E.coli but did not those of live E.coli. EMA-PCR could detect the DNA from live E.coli in mixed culture samples of live and dead E.coli at various ratio and there was no DNA amplification in only dead E.coli cultures. Similar results were observed in EMA real-time PCR. Further studies are needed to develop various EMA-PCR methods to detect viable waterborne pathogens such as Helicobacter pylori, Giardia lamblia, and so on.