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AG1031 induces apoptosis through suppressing SIRT1/p53 pathway in human neuroblastoma cells

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Abstract

Neuroblastoma is the most common extra-cranial tumor in childhood. As an antineoplastic medicine, the effect of AG-1031 on the neuroblastoma is still unclear. Silent information regulator 1 (SIRT1) is a conserved NAD+-dependent deacetylase, which plays a key role in carcinogenesis through the deacetylation of important regulatory proteins, including p53. The purpose of the present study was to determine whether there was a significant anti-tumor effect of AG-1031 on the human neuroblastoma cells through suppressing SIRT1/p53 pathway. Our study showed that AG1031 treatment resulted in a dose-dependent decrease in human neuroblastoma SH-SY5Y cell viability. The data, obtained from both Western blot assay and Hoechst 33258 staining, further showed that AG1031 exhibited strong anti-tumor activity closely associated with significantly increasing apoptotic indices and enhancing oxidative stress levels. Moreover, AG1031 treatment could down-regulate SIRT1 in a dose-dependent manner and up-regulate p53 acetylation, while overexpression of SIRT1 significantly attenuated the anti-tumor effect of AG1031 in SH-SY5Y cells. AG1031 potently induced SH-SY5Y cells apoptosis through suppressing SIRT1/p53 signaling. These data suggest that AG1031 may be used for therapeutic intervention in neuroblastoma treatment.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (31771148), National nature science foundation of Tianjin (14JCQNJC10500) and 111 Project (B08011).

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  1. College of Life Sciences and Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, 300071, People’s Republic of China

    Jingxuan Fu, Hui Zhang, Yuling Zhang & Tao Zhang

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  1. Jingxuan Fu
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Conceived and designed the experiments: JF, TZ. Performed the experiments and analyzed the data: JF, HZ, YZ. Wrote the manuscript: JF, TZ. Authors approved final version for publication.

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Correspondence to Tao Zhang.

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Fu, J., Zhang, H., Zhang, Y. et al. AG1031 induces apoptosis through suppressing SIRT1/p53 pathway in human neuroblastoma cells. Mol Cell Biochem 454, 165–175 (2019). https://doi.org/10.1007/s11010-018-3461-2

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