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Page 348 Seno et al. Cancer Drug Resist 2019;2:335-50 I http://dx.doi.org/10.20517/cdr.2019.01

drugs, the investigation of characteristic molecular mechanisms associated with apoptosis in CSCs, and the
development of novel strategies for the treatment of CSCs.

CSCs are crucial because they are involved in various pathological features of cancer. Thus, strategies for
CSC elimination and detailed understanding of CSCs are required to develop and effective treatment for
cancer. We proposed that miPS-CSCs established from miPSCs could be useful as models of CSCs for
investigating CSC properties in their niche and the formation of the tumor vasculature [8-11,47,48] . In this
study, topoisomerase II inhibitor, doxorubicin and daunorubicin, were found to be effective in suppressing
the growth of miPS-CSCs in vitro. In addition, detailed analyses of cell death mechanisms revealed that
daunorubicin-induced apoptosis of miPS-LLCcm cells was caspase-dependent but ICAD/CAD-independent
2+
2+
for DNA fragmentation. The endonuclease involved in this cell death appeared to be Ca /Mg -dependent.

DECLARATIONS
Acknowledgments
We thank SCADs, Japan, for providing compounds. We would like to thank Editage (www.editage.jp) for
English language editing.

Authors’ contributions
Made substantial contributions to conception and design of the study and performed data analysis and
interpretation: Seno A, Mizutani A, Masuda J, Seno M
Performed data acquisition, as well as provided administrative, technical, and material support: Seno A,
Mizutani A, Aizawa K, Onoue R, Ochi N, Taniguchi S, Sota T, Hiramoto Y, Michiue T, Nair N, Seno M

Availability of data and materials
Not applicable.

Financial support and sponsorship
This study was partly supported by the Grant-in-Aid for Scientific Research (A) (25242045) to Masaharu
S; the Grant-in-Aid for Challenging Exploratory Research (26640079) to Masaharu S from the Ministry of
Education, Sports and Culture, Japan and the Long-Range-Research-Initiative from Japan Chemical Industry
Association; Drug screening part in this study was supported by the Grant-in-Aid for Scientific Research (C)
(24501315) to Akifumi M.

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2019.

REFERENCES
1. Pattabiraman DR, Weinberg RA. Tackling the cancer stem cells - what challenges do they pose? Nat Rev Drug Discov 2014;13:497-
512.
2. Medema JP. Cancer stem cells: the challenges ahead. Nat Cell Biol 2013;15:338-44.