Abstract 22P
Background
Iron is an essential element for cell proliferation, growth and cellular activities. Iron has been shown to be important for tumorigenesis and metastasis. Therefore, targeting the metabolic pathways of iron can provide new tools for cancer treatment. In this study, effects of iron chelating ME0053, ME0055 and ME0192 salicylidene acylhydrazides were investigated in SH-SY5Y cells. By targeting iron in the cell, iron chelators are known to act on cyclins and CDKs, as well as on AKT and MAPK signaling which function in tumorigenesis. Therefore, in this study the effect of used iron chelators on cell viability was investigated both on MAPK and AKT signaling and on the mitotic Speedy/RINGO protein, which potentially regulates the communication of these two signaling paths. In addition, the apoptotic states of the cells were examined by active caspase-3 analysis.
Methods
Appropriate administration dose of the ME053, ME055 and ME0192 compounds was determined by MTT analysis and SH-SY5Y cells were treated with these compounds. Then, the effect of iron chelators on Speedy/RINGO expression, AKT and MAPK signaling and also on the apoptotic state of cells were determined by western blotting.
Results
These compounds have been shown to reduce the phosphorylation level of AKT, one of the signaling molecules associated with survival in SH-SY5Y cells. A relatively less but significant decrease in the activity of the MAPK signaling was observed. Besides, it has been demonstrated for the first time that Speedy/RINGO protein expression was significantly reduced by these compounds with an yet unknown mechanism. Finally, the active caspase-3 analysis in SH-SY5Y cells showed that the compounds ME0053, ME0055 and ME0192 increased the amount of active caspase-3 by 218%, 90% and 175%, respectively.
Conclusions
It was shown for the first time that ME0053, ME0055 and ME0192 compounds showed a suppressive effect on the MAPK and AKT pathways, and also on the anti-apoptotic protein Speedy/RINGO, thereby causing apoptotic death of SH-SY5Y cells.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
This work was supported by grant from the Mugla Sitki Kocman University Scientific Research Project Office (Project No: 17/023).
Disclosure
All authors have declared no conflicts of interest.