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

To identify a drug that can effectively eliminate these cancer stem cells (CSCs) and determine its mode of action. 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...

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Published in:Cancer drug resistance 2019-01, Vol.2 (2), p.335-350
Main Authors: Seno, Akimasa, Mizutani, Akifumi, Aizawa, Kazuki, Onoue, Ryoma, Masuda, Junko, Ochi, Naotaka, Taniguchi, Saki, Sota, Tatsuyuki, Hiramoto, Yuki, Michiue, Taisuke, Nair, Neha, Seno, Masaharu
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Language:English
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Summary:To identify a drug that can effectively eliminate these cancer stem cells (CSCs) and determine its mode of action. 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. 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 Ca -specific chelator, which suggested that CAD endonuclease does not contribute. Moreover, no obvious ICAD reduction/degradation was detected. 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.
ISSN:2578-532X
DOI:10.20517/cdr.2019.01