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

Year 2019, Volume: 78 Issue: 2, 83 - 88, 06.12.2019

Aysegul Yildiz

Abstract

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

Supporting Institution

This study was supported by grant to Ayşegül Yıldız from Mugla Sitki Kocman University Scientific Research Project Office, Research and Development Projects.

Project Number

17/023

Thanks

I would like to thank Assoc.Prof.Dr. Esin Sakallı ÇETİN from Muğla Sıtkı Koçman University, Faculty of Medicine, Medical Biology Department and Prof. Dr. Arzu KARABAY KORKMAZ from lstanbul Technical University, Faculty of Science and Letters, Molecular Biology and Genetics Department for allowing me to use their laboratory infrastructure. I also would like to thank Prof. Dr. Ömür BAYSAL from Muğla Sıtkı Koçman University, Faculty of Science, Molecular Biology and Genetics Department for his generous gift of acibenzolar-S-methyl (Syngenta).

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