https://scholars.lib.ntu.edu.tw/handle/123456789/597252
標題: | Selected ellipticine derivatives, known to target topoisomerase II, suppress the alternative lengthening of telomere (ALT) pathway in telomerase–negative cells | 作者: | Zencir S. Hsieh M.-H. Hsu J.-S. Ergun Y. Chou G.-L. TSAI-KUN LI Teng S.-C. Topcu Z. |
關鍵字: | Alternative lengthening of telomere; Anti-cancer therapeutics; DNA topoisomerase II; Ellipticine derivatives | 公開日期: | 2020 | 出版社: | Springer | 卷: | 146 | 期: | 7 | 起(迄)頁: | 1671-1676 | 來源出版物: | Journal of Cancer Research and Clinical Oncology | 摘要: | Background: DNA topoisomerase and telomerase enzymes are popular targets of several anti-tumor drugs. Smooth proceeding of telomeric recombination requires Topoisomerase II (Top2), which is involved in telomere-telomere recombination through functioning in relaxation of positive supercoils among the cells adopting telomerase-independent Alternative lengthening of telomere (ALT) pathway. Most of the inhibitors reported so far have been designed to targetsolely telomerase-positive cells, which can potentially lead to therapeutic failure because tumor cells treated with telomerase inhibitors can activate the ALT pathway for telomere maintenance. Knowing that ALT cells are more sensitive against a Top2 inhibitor, ICRF-93 agent, compared to telomerase-positive cells, we analyzed two selected ellipticine derivatives that we recently reported as TopII-targeting compounds, to assess their effects on the formation of DNA breaks and suppression of ALT pathway. Methods: Cell viability, Comet, C-Circle assays, dot blot, immunofluorescence staining, and telomere fluorescence in situ hybridization (FISH) staining were used for determining the effect of the compounds on ALT status of tumor cells. Results and conclusions: Treatment of ALT cells with ellipticine derivatives resulted in the formation of DNA breaks and suppression of ALT-associated phenotypes in vitro. Our results will contribute to the development of therapeutic strategies combining telomerase and ALT pathway inhibitors. ? 2020, Springer-Verlag GmbH Germany, part of Springer Nature. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85083865035&doi=10.1007%2fs00432-020-03213-x&partnerID=40&md5=3cb27938211bd61c6a41beb6bccedc1b https://scholars.lib.ntu.edu.tw/handle/123456789/597252 |
ISSN: | 0171-5216 | DOI: | 10.1007/s00432-020-03213-x | SDG/關鍵字: | antineoplastic agent; DNA topoisomerase (ATP hydrolysing); ellipticine; ellipticine derivative; icrf 93; telomerase inhibitor; unclassified drug; antineoplastic agent; ellipticine derivative; gyrase inhibitor; telomerase; ALT cell line; Article; cell viability; comet assay; controlled study; cytotoxicity; DNA strand breakage; drug selectivity; female; fluorescence in situ hybridization; human; human cell; immunofluorescence; MTS assay; phenotype; priority journal; SaOS-2 cell line; telomere length; cell line; chemistry; drug effect; fluorescent antibody technique; genetics; telomere homeostasis; Antineoplastic Agents; Cell Line; Ellipticines; Fluorescent Antibody Technique; Humans; In Situ Hybridization, Fluorescence; Telomerase; Telomere Homeostasis; Topoisomerase II Inhibitors |
顯示於: | 微生物學科所 |
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