in vivo Mechanisms of Novel Selective Fluorescent Leukemia Stem Cell Inhibitor
| Project/Area Number |
15K15051
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
General pharmacology
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| Research Institution | Mie University |
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Principal Investigator |
Tanaka Toshio 三重大学, 医学(系)研究科(研究院), 教授 (00135443)
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| Co-Investigator(Kenkyū-buntansha) |
Nishimura Yuhei 三重大学, 大学院医学系研究科, 准教授 (30303720)
Kawase Reiko 三重大学, 大学院医学系研究科, 助教 (50746740)
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| Project Period (FY) |
2015-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
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| Keywords | ヒトがん幹細胞阻害薬 / ZM-B708 / 悪性腫瘍治療抵抗性 / ヒトがん幹細胞治療薬 / ゼブラフィッシュ / 免疫不全マウス / 蛍光試薬 / がん幹細胞選択性 |
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| Outline of Final Research Achievements |
Elimination of leukemia stem cells is necessary for the destruction of malignant cell populations. Using the LSC-xenograft zebrafish screening method we previously developed, we found that the fluorescent compound DiOC5(3) selectively marked LSCs and suppressed their proliferation in vivo and in vitro. DiOC5(3) had no obvious toxicity to human umbilical cord blood CD34+ progenitor cells and normal zebrafish. It accumulated in mitochondria through organic anion transporter polypeptides that are overexpressed in the plasma membrane of LSCs, and induced apoptosis via ROS overproduction. DiOC5(3) also inhibited the nuclear translocation of NF-κB through the downregulation of LSC-selective pathways, as indicated from DNA microarray analysis. In summary, DiOC5(3) is a new type of anti-LSC compound available for diagnostic imaging and therapeutics that has the advantage of being a single fluorescent chemical.
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Report
(2 results)
Research Products
(16 results)
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[Journal Article] In Vivo Detection of Mitochondrial Dysfunction Induced by Clinical Drugs and Disease-Associated Genes Using a Novel Dye ZMJ214 in Zebrafish.2016
Author(s)
Sasagawa S, Nishimura Y, Koiwa J, Nomoto T, Shintou T, Murakami S, Yuge M, Kawaguchi K, Kawase R, Miyazaki T, Tanaka T.
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Journal Title
ACS Chem Biol.
Volume: 11
Pages: 381-388
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Comparative study of the zebrafish embryonic toxicity test and mouse embryonic stem cell test to screen developmental toxicity of human pharmaceutical drugs2016
Author(s)
Atsuto Inoue, Yuhei Nishimura, Norihito Matsumoto, Noriko Umemoto , Yasuhito Shimada, Toru Maruyama, Kana Kayasuga, Motohiko Morihara, Jun Katagi, Tsutomu Shiroya, Yasushi Hirota, Soonih Kim , Toshio Tanaka
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Journal Title
Fundamental Toxicological Sciences
Volume: 3
Pages: 79-87
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Systems pharmacology of adiposity reveals inhibition of EP300 as a common therapeutic mechanism of caloric restriction and resveratrol for obesity.2015
Author(s)
Nishimura Y, Sasagawa S, Ariyoshi M, Ichikawa S, Shimada Y, Kawaguchi K, Kawase R, Yamamoto R, Uehara T, Yanai T, Takata R, Tanaka T.
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Journal Title
Front Pharmacol.
Volume: 6
DOI
Related Report
Peer Reviewed / Open Access
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