Daunorubicin can eliminate iPS-derived cancer stem cells via ICAD/CAD-independent DNA fragmentation

Akimasa Seno, Akifumi Mizutani, Kazuki Aizawa, Ryoma Onoue, Junko Masuda, Naotaka Ochi, Saki Taniguchi, Tatsuyuki Sota, Yuki Hiramoto, Taisuke Michiue, Neha Nair, Masaharu Seno

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Aim: To identify a drug that can effectively eliminate these cancer stem cells (CSCs) and determine its mode of action. Methods: CSCs were obtained from mouse induced pluripotent stem cells (miPSCs) using cancer cell-conditioned media. Drug screening was performed on these cells or after transplantation into mice. Apoptosis was analyzed by flow cytometry and western blotting. Results: Drug screening studies showed that daunorubicin, a topoisomerase II inhibitor, is specifically cytotoxic to miPS-CSCs. Daunorubicin-induced apoptosis was found to be associated with p53 accumulation, activation of the caspase cascade, and oligonucleosomal DNA fragmentation. Treatment with the caspase inhibitor abolished daunorubicin-induced DNA fragmentation and was therefore considered to act downstream of caspase activation. This was also suppressed by treatment with a Ca2+-specific chelator, which suggested that CAD endonuclease does not contribute. Moreover, no obvious ICAD reduction/degradation was detected. Conclusion: Daunorubicin effectively eliminated CSCs, which are dependent on the p53/caspase signaling cascade. The current findings provided the basis for further studies on CSC-targeted drugs for the development of cancer treatment strategies.

Original languageEnglish
Pages (from-to)335-350
Number of pages16
JournalCancer Drug Resistance
Volume2
Issue number2
DOIs
Publication statusPublished - 2019

Keywords

  • Cancer stem cell
  • Daunorubicin
  • DNA fragmentation

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology (medical)

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