Acibenzolar-S-Methyl Inhibits MEK1/2 Signaling in SH-SY5Y Neuroblastoma Cells

Objective: Targeted cancer therapy using targeted cell proliferation inhibitors has become increasingly more critical. Studies conducted over the last decade have shown that non-steroidal drugs containing salicylic acid (SA) such as aspirin reduce mortality in many cancers. From this perspective, there are data suggesting SA as a potential inhibitor of the mitogenic MEK1/2 (mitogen-activated-protein-kinase, MAPK), extracellular-signal regulated-protein-kinase (ERK)) signaling, which could be highly effective in the prevention of proliferation in cancer. To date, no study has been conducted on the effect of SA on MEK1/2 signaling in neuroblastoma cells. Thus, the aim of this study is to reveal whether SA has an effect on MEK1/2 signaling in neuroblastoma cancer which is a frequent pediatric cancer with poor prognosis. Materials and Methods: The purpose of this study was to investigate whether a SA analog acibenzolar-S-methyl had an effect on the MEK1/2 signaling pathway and on cell viability in SH-SY5Y neuroblastoma cells by MTS (3-(4,5-dimethylthiazol2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) cell viability analysis and MEK1/2 and active caspase-3 detection by western blotting technique. Results: MTS cell viability test indicated that 10 mM acibenzolar-S-methyl reduces cell viability by 50%. Western blotting results of 10 mM acibenzolar-S-methyl–treated cells showed that MEK1/2 signaling was significantly inhibited in SH-SY5H cells. Besides, an increase in active-caspase-3 levels provided insight into acibenzolar-S-methyl’s apoptotic effect which needs further morphological apoptotic data. Conclusion: Our research is the first to show that SA analog acibenzolar-S-methyl negatively affects MEK1/2 signaling causing the death of SH-SY5Y neuroblastoma cells. Our results can give insight not only into understanding the mechanisms of carcinogenesis but also into developing effective treatment methods.

Keywords:

Salicylic acid, Acibenzolar-S-Methyl, MEK1/2, SH-SY5Y neuroblastoma cancer,

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