NDLI: Pro-differentiating effects of a synthetic flavagline on human teratocarcinomal cancer stem-like cells

Content Provider	Springer Nature Link
Author	Emhemmed, Fathi Ali Azouaou, Sarah Zhao, Qian Appert Collin, Aline Bennasroune, Amar Schini Kerth, Valérie B. Muller, Christian D. Désaubry, Laurent Fuhrmann, Guy
Copyright Year	2016
Abstract	As initiators of the carcinogenic process, cancer stem cells (CSCs) are considered as new targets for anti-cancer therapies. However, these cells are hidden in the cancer bulk and remain relatively insensitive to chemotherapy, which targets their proliferative capacities. Alternatively, growing evidences have pointed out that a differentiation therapy could adversely affect these cells, which consequently should lose their self-renewal properties and become less aggressive. In order to evaluate the differentiation potential of an emerging class of anti-cancer drugs, we used the poorly differentiated teratocarcinomal cell as a model of Oct4-expressing CSC and determined the molecular mechanisms induced by the highly active flavagline FL3. The drug, administrated at sublethal concentration and for long period, was able to downregulate the expression levels of the stemness factors Oct4 and Nanog at both transcriptional and translational levels, concomitantly with a decrease of clonogenicity. The appearance of specific neural markers further demonstrated the differentiation properties of FL3. Interestingly, an expression of active caspase-3 and an upregulation of the expression of the germ cell nuclear factor were observed in treated cells; this suggests that the suppression of Oct4 expression required for the induction of differentiation involves overlapping mechanisms of protein degradation and gene repression. Finally, this study shows that FL3, like all-trans retinoic acid (ATRA), acts as a differentiation inducer of teratocarcinomal cells. Thus, FL3 offers an alternative possibility for cancer treatment since it could target the carcinogenic process by inducing the differentiation of ATRA-resistant and Oct4-expressing CSCs, without toxic side effects on normal cells.
Starting Page	295
Ending Page	306
Page Count	12
File Format	PDF
ISSN	07422091
Journal	Cell Biology and Toxicology
Volume Number	33
Issue Number	3
e-ISSN	15736822
Language	English
Publisher	Springer Netherlands
Publisher Date	2016-12-15
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Cancer stem cells Differentiation Flavagline Oct4 Teratocarcinoma Cell Biology Pharmacology/Toxicology Biochemistry
Content Type	Text
Resource Type	Article
Subject	Cell Biology Health, Toxicology and Mutagenesis Toxicology

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