Please use this identifier to cite or link to this item: https://hdl.handle.net/11147/10245
Title: Identification of a noncanonical necrotic cell death triggered via enhanced proteolysis by a novel sapogenol derivative
Authors: Üner, Göklem
Tağ, Özgür
Erzurumlu, Yalçın
Ballar Kırmızıbayrak, Petek
Bedir, Erdal
Üner, Göklem
Bedir, Erdal
Izmir Institute of Technology. Biotechnology and Bioengineering
Issue Date: 2020
Publisher: American Chemical Society
Abstract: Small molecules which activate distinct cell death pathways have promising high potential for anticancer drug research. Especially, regulated necrosis draws attention as an alternative cell death mechanism to overcome the drug resistance. Here, we report that a new semisynthetic saponin analogue (AG-08) triggers necrotic cell death with unprecedented pathways. AG-08-mediated necrosis depends on enhanced global proteolysis involving calpains, cathepsins, and caspases. Moreover, AG-08 generates several alterations in lysosomal function and physiology including membrane permeabilization, redistribution toward the perinuclear area, and lastly excessive tubulation. As a consequence of lysosomal impairment, the autophagic process was abolished via AG-08 treatment. Collectively, in addition to its ability to induce necrotic cell death, which makes AG-08 a promising candidate to cope with drug resistance, its unique activity mechanisms including autophagy/lysosome impairment and enhancement of proteolysis leading a strong death capacity emphasizes its potential for anticancer drug research. ©
Description: PubMed: 33136369
URI: https://doi.org/10.1021/acs.chemrestox.0c00339
https://hdl.handle.net/10245
ISSN: 0893-228X
Appears in Collections:PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection

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