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

Abstract

Objective: Targeted cancer therapy using targeted cell proliferation inhibitors has become increasingly more critical. Studiesconducted over the last decade have shown that non-steroidal drugs containing salicylic acid (SA) such as aspirin reducemortality in many cancers. From this perspective, there are data suggesting SA as a potential inhibitor of the mitogenicMEK1/2 (mitogen-activated-protein-kinase, MAPK), extracellular-signal regulated-protein-kinase (ERK)) signaling, whichcould be highly effective in the prevention of proliferation in cancer. To date, no study has been conducted on the effect ofSA on MEK1/2 signaling in neuroblastoma cells. Thus, the aim of this study is to reveal whether SA has an effect on MEK1/2signaling 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 aneffect on the MEK1/2 signaling pathway and on cell viability in SH-SY5Y neuroblastoma cells by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) cell viability analysis and MEK1/2 and active caspase-3detection by western blotting technique.Results: MTS cell viability test indicated that 10 mM acibenzolar-S-methyl reduces cell viability by 50%. Western blottingresults of 10 mM acibenzolar-S-methyl–treated cells showed that MEK1/2 signaling was significantly inhibited in SH-SY5Hcells. Besides, an increase in active-caspase-3 levels provided insight into acibenzolar-S-methyl’s apoptotic effect whichneeds further morphological apoptotic data.Conclusion: Our research is the first to show that SA analog acibenzolar-S-methyl negatively affects MEK1/2 signalingcausing the death of SH-SY5Y neuroblastoma cells. Our results can give insight not only into understanding the mechanismsof carcinogenesis but also into developing effective treatment methods.