20.500.12556/RUL-135019 Cytotoxic activity of LLO Y406A is targeted to the plasma membrane of cancer urothelial cells Identification of novel agents for bladder cancer treatment is highly desirable due to the high incidence of tumor recurrence and the risk of progression to muscle-invasive disease. The key feature of the cholesterol-dependent toxin listeriolysin O mutant (LLO Y406A) is its preferential activity at pH 5.7, which could be exploited either directly for selective targeting of cancer cells or the release of accumulated therapeutics from acidic endosomes. Therefore, our goal was to compare the cytotoxic effect of LLO Y406A on cancer cells (RT4) and normal urothelial cells (NPU), and to identify which cell membranes are the primary target of LLO Y406A by viability assays, life-cell imaging, fluorescence, and electron microscopy. LLO Y406A decreased viability, altered cell morphology, provoked membrane blebbing, and induced apoptosis in RT4 cells, while it did not affect NPU cells. LLO Y406A did not cause endosomal escape in RT4 cells, while the plasma membrane of RT4 cells was revealed as the primary target of LLO Y406A. It has been concluded that LLO Y406A has the ability to selectively eliminate cancer urothelial cells through pore-forming activity at the plasma membrane, without cytotoxic effects on normal urothelial cells. This promising selective activity merits further testing as an anti-cancer agent. bladder cancer cancer urothelial cells normal urothelial cells listeriolysin O blebbing calcium influx pore-forming toxin cytolysin cytotoxicity biokemija rakave celice listeriolizin O toksini true false true Angleški jezik Slovenski jezik Članek v reviji 2022-02-17 12:45:28 2022-02-17 12:45:29 2022-09-14 04:11:13 0000-00-00 00:00:00 2021 0 0 15 str. iss. 7, art. 3305 Vol. 22 Apr. 2021 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 577 1422-0067 10.3390/ijms22073305 57572867 RAZ_Resnik_Natasa_2021.pdf RAZ_Resnik_Natasa_2021.pdf 1 D79667A5CCF1827ABF29F161F4BED822 e8eb52a6a750259ea13a7c6829c1c311784632a9155dd3ef69ad1c7e004fb76d 6ff41683-8fe7-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=153840 https://www.mdpi.com/1422-0067/22/7/3305 1 dc56769f-8fe6-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=153839 Medicinska fakulteta 0 0 0