Reference : Cytostatic hydroxycoumarin OT52 induces ER/Golgi stress and STAT3 inhibition triggeri...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Systems Biomedicine
http://hdl.handle.net/10993/37389
Cytostatic hydroxycoumarin OT52 induces ER/Golgi stress and STAT3 inhibition triggering non-canonical cell death and synergy with BH3 mimetics in lung cancer.
English
Lee, JY []
Talhi, O []
Jang, D []
Cerella, C []
Gaigneaux, Anthoula mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Kim, KW []
Lee, JW []
Dicato, M []
Bachari, K []
Han, BW []
Silva, AMS []
Orlikova, B []
Diederich, M []
Mar-2018
Cancer Letters
Elsevier
Yes (verified by ORBilu)
International
0304-3835
1872-7980
Limerick
Netherlands
[en] Coumarins are natural compounds with antioxidant, anti-inflammatory and anti-cancer potential known to modulate inflammatory pathways. Here, non-toxic biscoumarin OT52 strongly inhibited proliferation of non-small cell lung cancer cells with KRAS mutations, inhibited stem-like characteristics by reducing aldehyde dehydrogenase expression and abrogated spheroid formation capacity. This cytostatic effect was characterized by cell cycle arrest and onset of senescence concomitant with endoplasmic reticulum and Golgi stress, leading to metabolic alterations. Mechanistically, this cellular response was associated with the novel capacity of biscoumarin OT52 to inhibit STAT3 transactivation and expression of its target genes linked to proliferation. These results were validated by computational docking of OT52 to the STAT3 DNA-binding domain. Combination treatments of OT52 with subtoxic concentrations of Bcl-xL and Mcl-1-targeting BH3 protein inhibitors triggered synergistic immunogenic cell death validated in colony formation assays as well as in vivo by zebrafish xenografts.
Researchers
http://hdl.handle.net/10993/37389
10.1016/j.canlet.2017.12.007

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