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

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

机构地区：[1]Laboratory of Nano-Biotechnology,Graduate School of Interdisciplinary Science and Engineering in Health Systems,Okayama University,Okayama 700-8530,Japan [2]Division of Medical Bioengineering,Graduate School of Natural Science and Technology,Okayama University,Okayama 700-8530,Japan.

出　　处：《Cancer Drug Resistance》2019年第2期335-350,共16页癌症耐药（英文）

摘　　要：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.

关 键 词：DAUNORUBICIN cancer stem cell DNA fragmentation 

分 类 号：R73[医药卫生—肿瘤]