Publication List English

New photic stimulating system with white light-emitting diodes to elicit electroretinograms from zebrafish larvae.

Potential protective function of the sterol regulatory element binding factor 1-fatty acid desaturase 12 axis in early-stage age-related macular degeneration

Activation of Sterol Regulatory Element Binding Factors by Fenofibrate and Gemfibrozil Stimulates Myelination in Zebrafish

Downregulation of GSTK1 Is a Common Mechanism Underlying Hypertrophic Cardiomyopathy

Comparative Transcriptome Analysis Identifies CCDC80 as a Novel Gene Associated with Pulmonary Arterial Hypertension

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


Beibei Zhanga, Yasuhito Shimada, Junya Kuroyanagia, Michiko Ariyoshia, Tsuyoshi Nomotof, Taichi Shintouf, Noriko Umemotoa, b, Yuhei Nishimura, Takeshi Miyazakif, Toshio Tanaka
doi:10.1016/j.biomaterials.2015.02.009 Volume 52, June 2015, Pages 14-25

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Œ-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-ƒΘB 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.