Format

Send to

Choose Destination
Mol Cell Biochem. 2019 Apr;454(1-2):165-175. doi: 10.1007/s11010-018-3461-2. Epub 2018 Oct 22.

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

Author information

1
College of Life Sciences and Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, 300071, People's Republic of China.
2
College of Life Sciences and Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, 300071, People's Republic of China. zhangtao@nankai.edu.cn.

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.

KEYWORDS:

AG1031; Apoptosis; Neuroblastoma; Overexpression; SIRT1; p53

PMID:
30350304
DOI:
10.1007/s11010-018-3461-2
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center