Original scientific paper
https://doi.org/10.2478/aiht-2022-73-3688
Cytotoxicity-related effects of imidazolium and chlorinated bispyridinium oximes in SH-SY5Y cells
Antonio Zandona
; Institute for Medical Research and Occupational Health, Zagreb, Croatia
Tamara Zorbaz
; Institute for Medical Research and Occupational Health, Zagreb, Croatia
Katarina Miš
; University of Ljubljana Faculty of Medicine, Institute of Pathophysiology, Ljubljana, Slovenia
Sergej Pirkmajer
; University of Ljubljana Faculty of Medicine, Institute of Pathophysiology, Ljubljana, Slovenia
Maja Katalinić
orcid.org/0000-0001-7043-4291
; Institute for Medical Research and Occupational Health, Zagreb, Croatia
Abstract
Current research has shown that several imidazolium and chlorinated bispyridinium oximes are cytotoxic and activate different mechanisms or types of cell death. To investigate this further, we analysed interactions between these oximes and acetylcholine receptors (AChRs) and how they affect several signalling pathways to find a relation between the observed toxicities and their effects on these specific targets. Chlorinated bispyridinium oximes caused time-dependent cytotoxicity by inhibiting the phosphorylation of STAT3 and AMPK without decreasing ATP and activated ERK1/2 and p38 MAPK signal cascades. Imidazolium oximes induced a time-independent and significant decrease in ATP and inhibition of the ERK1/2 signalling pathway along with phosphorylation of p38 MAPK, AMPK, and ACC. These pathways are usually triggered by a change in cellular energy status or by external signals, which suggests that oximes interact with some membrane receptors. Interestingly, in silico analysis also indicated that the highest probability of interaction for all of our oximes is with the family of G-coupled membrane receptors (GPCR). Furthermore, our experimental results showed that the tested oximes acted as acetylcholine antagonists for membrane AChRs. Even though oxime interactions with membrane receptors need further research and clarification, our findings suggest that these oximes make promising candidates for the development of specific therapies not only in the field of cholinesterase research but in other fields too, such as anticancer therapy via altering the Ca2+ flux involved in cancer progression.
Keywords
antidotes; calcium signalling; cell viability; Fura-2 AM; receptor; kinase
Hrčak ID:
288097
URI
Publication date:
28.12.2022.
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