https://scholars.lib.ntu.edu.tw/handle/123456789/518223
標題: | Direct evidence of mitochondrial G-quadruplex DNA by using fluorescent anti-cancer agents | 作者: | Huang W.-C. Tseng T.-Y. Chen Y.-T. Chang C.-C. Wang Z.-F. Wang C.-L. Hsu T.-N. Li P.-T. C. T. Chen JING-JER LIN PEI-JEN LOU Chang T.-C. |
公開日期: | 2015 | 出版社: | Oxford University Press | 卷: | 43 | 期: | 21 | 起(迄)頁: | 10102-10113 | 來源出版物: | Nucleic Acids Research | 摘要: | G-quadruplex (G4) is a promising target for anticancer treatment. In this paper, we provide the first evidence supporting the presence of G4 in the mitochondrial DNA (mtDNA) of live cells. The molecular engineering of a fluorescent G4 ligand, 3, 6- bis(1-methyl-4-vinylpyridinium) carbazole diiodide (BMVC), can change its major cellular localization from the nucleus to the mitochondria in cancer cells, while remaining primarily in the cytoplasm of normal cells. A number of BMVC derivatives with sufficient mitochondrial uptake can induce cancer cell death without damaging normal cells. Fluorescence studies of these anti-cancer agents in live cells and in isolated mitochondria from HeLa cells have demonstrated that their major target is mtDNA. In this study, we use fluorescence lifetime imaging microscopy to verify the existence of mtDNA G4s in live cells. Bioactivity studies indicate that interactions between these anti-cancer agents and mtDNA G4 can suppress mitochondrial gene expression. This work underlines the importance of fluorescence in the monitoring of drug-target interactions in cells and illustrates the emerging development of drugs in which mtDNA G4 is the primary target. ? The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84963887539&doi=10.1093%2fnar%2fgkv1061&partnerID=40&md5=38cbff5cc3ea0ce4f6a3663c0770402b https://scholars.lib.ntu.edu.tw/handle/123456789/518223 |
ISSN: | 0305-1048 | DOI: | 10.1093/nar/gkv1061 | SDG/關鍵字: | 3,6 bis(1 methyl 2 vinylpyridinium)carbazole diiodide; 3,6 bis(1 methyl 4 vinylpyridinium iodide) 9 [1 (1 methyl piperidinium iodide)dodecyl]carbazole; 3,6 bis(1 methyl 4 vinylpyridinium)carbazole diiodide; antineoplastic agent; guanine quadruplex; mitochondrial DNA; unclassified drug; 3,6-bis(1-methyl-2-vinylpyridinium)carbazole; antineoplastic agent; carbazole derivative; fluorescent dye; guanine quadruplex; mitochondrial DNA; o-BMVC-12C-P; pyridinium derivative; animal experiment; animal model; antineoplastic activity; Article; cancer cell; cell death; cell nucleus; controlled study; cytoplasm; DNA determination; drug DNA interaction; drug structure; fluorescence; gene expression; HeLa cell line; lung cancer; mitochondrial gene; mitochondrion; mouse; nonhuman; priority journal; tumor xenograft; animal; Bagg albino mouse; cell line; chemistry; fluorescence microscopy; human; Animals; Antineoplastic Agents; Carbazoles; Cell Line; DNA, Mitochondrial; Fluorescent Dyes; G-Quadruplexes; HeLa Cells; Humans; Mice, Inbred BALB C; Microscopy, Fluorescence; Pyridinium Compounds |
顯示於: | 醫學系 |
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