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In vivo selective imaging and inhibition of leukemia stem-like cells using the fluorescent carbocyanine derivative, DiOC5(3)

Author:
Zhang, Beibei, Shimada, Yasuhito, Kuroyanagi, Junya, Ariyoshi, Michiko, Nomoto, Tsuyoshi, Shintou, Taichi, Umemoto, Noriko, Nishimura, Yuhei, Miyazaki, Takeshi, Tanaka, Toshio
Source:
Biomaterials 2015 v.52 pp. 14-25
ISSN:
0142-9612
Subject:
DNA microarrays, Danio rerio, apoptosis, blood, cell culture, fluorescence, fluorescent substances, gene expression regulation, humans, image analysis, iodides, leukemia, microarray technology, mitochondria, neoplasm cells, plasma membrane, polypeptides, screening, stem cells, toxicity, transcription factor NF-kappa B, umbilical cord, xenotransplantation
Abstract:
Elimination of leukemia stem cells (LSCs) is necessary for the destruction of malignant cell populations. Owing to the very small number of LSCs in leukemia cells, xenotransplantation studies are difficult in terms of functionally and pathophysiologically replicating clinical conditions of cell culture experiments. There is currently a limited number of lead compounds that target LSCs. Using the LSC-xenograft zebrafish screening method we previously developed, we found that the fluorescent compound 3,3′-dipentyloxacarbocyanine iodide (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.
Agid:
6034842