• Title/Summary/Keyword: topoisomerase $II{\alpha}$

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Topoisomerase I and II Inhibitory Activities and Cytotoxic Constituents from the Barks of Tilia amurnesis

  • Piao, Dong Gen;Lee, You-Jeong;Seo, Chang-Seob;Lee, Chong-Soon;Kim, Jae-Ryong;Chang, Hyun-Wook;Son, Jong-Keun
    • Natural Product Sciences
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    • v.17 no.3
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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.

Isolation and Structure Determination of Cytotoxic Compounds with Topoisomerse I and II Inhibitory Activity from the spikes of Prunella vulgaris var. lilaeina

  • Byun, S.J.;Lee, J.E.;Son, J.K.;Lee, J.S.;Lee, S.H.;Park, Y.S.;Woo, M.H.
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.370.1-370.1
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    • 2002
  • Prunella vulgaris var. lilacina (Labiatae) has been used as a Korean traditional medicine for the treatment of. fever. inflammation. urinary disadvantage and cancer. We previously isolated three $\alpha$-amyrin triterpenoids from n-butanol-I extract. They are 3$\alpha$-hydroxyurs-12-ene-28-oic acid (ursolic acid). 2$\alpha$, 3$\alpha$-dihydroxyurs-12-ene-28-oic acid and 2$\alpha$. 3$\alpha$. 19$\alpha$ trihydroxyurs-12-ene-28-oic acid (euscaphic acid) exhibiting cytotoxicity and topoisomerase I inhibition. (omitted)

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Predictive Factors Determining Neoadjuvant Chemotherapy Outcomes in Breast Cancer - a Single Center Experience

  • Yu, Yang;Xiang, Hua;He, Xiang-Ming;Yang, Hong-Jian;Zong, Xiang-Yun
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.4
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    • pp.2401-2406
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    • 2013
  • From January 1, 2008 to March 31, 2010, 101 patients with stage II-III breast cancer were enrolled in this study and subjected to an anthracycline-based neoadjuvant chemotherapy regimen with or without docetaxel. Surgery was performed after 2-6 cycles of chemotherapy, and the clinical response was determined by pathological and histochemical assessments. The clinical response rate, as indicated by complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD), were 6.9, 52.5, 36.6, and 4.0%, respectively. A multivariable correlation analysis indicated that the overall clinical response rate correlated with the number of metastatic lymph nodes, number of chemotherapy cycles, and vessel invasion status. Importantly, the CR rate was only associated with the number of chemotherapy cycles. Nonparametric tests failed to detect a correlation between HER2 or Topo $II{\alpha}$ status and clinical response to neoadjuvant chemotherapy in these patients. When they were stratified by HER2 or HR status, for HER2-positive patients the CR rate was associated with vessel invasion and Topo $II{\alpha}$ status. Based on our findings, we propose that HR, HER-2 and Topo $II{\alpha}$ are not putative predictive biomarkers of chemotherapy outcome for breast cancer patients. Topo $II{\alpha}$ expression level was only inversely correlated with CR rate among HR-positive patients. Importantly, the achievement of CR was largely related to the number of chemotherapy cycles.

Estrogen Receptor α Roles in Breast Cancer Chemoresistance

  • Xu, Chao-Yang;Jiang, Zhi-Nong;Zhou, Ying;Li, Jia-Jia;Huang, Li-Ming
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.7
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    • pp.4049-4052
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    • 2013
  • Resistance to chemotherapy treatment, which may lead to limited efficacy of systemic therapy in breast cancer patients, is multifactorial. Among the mechanisms of resistance to chemotherapy treatment, there are those closely related to estrogen receptor ${\alpha}$, P-glycoprotein, multidrug resistance-related protein, glutathione S-transferase pi and topoisomerase-II. $ER{\alpha}$ is ligand-activated transcription factor that regulates gene expression and plays a critical role in endocrine signaling. In previous preclinical and clinical studies, positive $ER{\alpha}$ expression in breast cancer cells was correlated with decreased sensitivity to chemotherapy. This article reviews current knowledge on the predictive value of $ER{\alpha}$ with regard to response to chemotherapy. Better understanding of its role may facilitate patient selection of therapeutic regimens and lead to optimal clinical outcomes.

Identification of Mutations in Protein Kinase CKIIβ Subunit That Affect Its Binding to Ribosomal Protein L41 and Homodimerization

  • Ahn, Bong-Hyun;Lee, Ji-Hoon;Bae, Young-Seuk
    • BMB Reports
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    • v.36 no.4
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    • pp.344-348
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    • 2003
  • Protein kinase CKII is composed of two catalytic ($\alpha$ or $\alpha$') subunits and two regulatory ($\beta$) subunits. The $CKII{\beta}$ subunit is thought to mediate the tetramer formation and interact with other target proteins. However, its physiological function remains obscure. In this study, point mutants of $CKII{\beta}$ that are defective for the L41 binding were isolated by using the reverse two-hybrid system. A sequence analysis of the point mutants revealed that Asp-26, Met-52, and Met-78 of $CKII{\beta}$ are critical for L41 binding; Asn-67 (and/or Lys-139) and Met-52 are important for $CKII{\beta}$ homodimerization. Two point mutants, R75 and R83, of $CKII{\beta}$ interacted with L5, topoisomerase $II{\beta}$, and CKBBP1/SAG, but not with the wild-type $CKII{\beta}$. This indicates that $CKII{\beta}$ homodimerization is not a prerequisite for its binding to target proteins. These $CKII{\beta}$ point mutants may be useful in exploring the biochemical physiological functions of $CKII{\beta}$.

Mithramycin Inhibits Etoposide Resistance in Glucose-deprived HT-29 Human Colon Carcinoma Cells

  • Lee, Eun-Mi;Park, Hae-Ryong;Hwang, Ji-Hwan;Park, Dong-Jin;Chang, Kyu-Seob;Kim, Chang-Jin
    • Journal of Microbiology and Biotechnology
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    • v.17 no.11
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    • pp.1856-1861
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    • 2007
  • Physiological cell conditions such as glucose deprivation and hypoxia play roles in the development of drug resistance in solid tumors. These tumor-specific conditions cause decreased expression of DNA topoisomerase $II{\alpha}$, rendering cells resistant to topo II target drugs such as etoposide. Thus, targeting tumor-specific conditions such as a low glucose environment may be a novel strategy in the development of anticancer drugs. On this basis, we established a novel screening program for anticancer agents with preferential cytotoxic activity in cancer cells under glucose-deprived conditions. We recently isolated an active compound, AA-98, from Streptomyces sp. AA030098 that can prevent stress-induced etoposide resistance in vitro. Furthermore, LC-MS and various NMR spectroscopic methods identified AA-98 as mithramycin, which belongs to the aureolic acid group of antitumor compounds. We found that mithramycin prevents the etoposide resistance that is induced by glucose deprivation. The etoposide-chemosensitive action of mithramycin was just dependent on strict low glucose conditions, and resulted in the selective cell death of etoposide-resistant HT-29 human colon cancer cells.

Cloning and Characterization of Replication Origins from Misgurnus mizolepis (미꾸라지로부터의 복제원점 클로닝 및 그 특성에 관한 연구)

  • Lim Hak-Seob;Kim Moo-Sang;Lee Hyung-Ho
    • Journal of Aquaculture
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    • v.8 no.3
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    • pp.209-220
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    • 1995
  • The nuclear matrix was isolated from Misgumus mizolepis liver nuclei by low salt extraction and restriction enzyme treatment. The structure was digested with proteinase K. After centrifugation, matrix attachment regions (MARs) were obtained by RNase treatment and phenol-chloroform extraction. The result leads to the appearance of smeared bands in the range of about 0.3-15 kb. pURY19 vector was constructed by inserting 2.13 kb Eco47 III fragment of the yeast uracil 3 gene into the unique Ssp I site of pUC19 plasmid vector as a selection marker. This vector is unable to be maintained in Sacrharomyces cerevisiae by itself since it cannot replicate as an extrachromosomal element. Using this system, we attempted cloning the ARS (autonomously replicating sequence) from M. mizelepis to develop an efficient expression vector for the transgenic fish. pURY19N_{l-62}$ were constructed by inserting MARs in pURY19 plasmid vector and transformation of E. coli $DH5\alpha$. Replication origins (ARS) of M. mizolepis were isolated, which enabled the vector to replicate autonomously in S. cerevisiae. The cloned DNA fragments were sequenced by Sanger's dideoxy-chain termination method. All clones were AT-rich. $pURY19N_6$, one of the clones, expecially contained ARS consensus sequence, Topoisomerase II consensus, near A-box and T-box.

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