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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 |
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. © | URI: | https://doi.org/10.1021/acs.chemrestox.0c00339 https://hdl.handle.net/11147/10245 |
ISSN: | 0893-228X |
Appears in Collections: | Bioengineering / Biyomühendislik PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection |
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acs.chemrestox.0c00339.pdf | 7.6 MB | Adobe PDF | View/Open |
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