TIGAR knockdown enhanced the anticancer effect of aescin via regulating autophagy and apoptosis in colorectal cancer cells

Acta Pharmacologica Sinica
Bin LiQuan-Gen Gao

Abstract

Our previous study showed that TP53-induced glycolysis and apoptosis regulator (TIGAR) regulated ROS, autophagy, and apoptosis in response to hypoxia and chemotherapeutic drugs. Aescin, a triterpene saponin, exerts anticancer effects and increases ROS levels. The ROS is a key upstream signaling to activate autophagy. Whether there is a crosstalk between TIGAR and aescin in regulating ROS, autophagy, and apoptosis is unknown. In this study, we found that aescin inhibited cell viability and colony formation, and induced DNA damage, cell cycle arrest, and apoptosis in cancer cell lines HCT-116 and HCT-8 cells. Concurrently, aescin increased the expression of TIGAR, ROS levels, and autophagy activation. Knockdown of TIGAR enhanced the anticancer effects of aescin in vitro and in vivo, whereas overexpression of TIGAR or replenishing TIGAR downstream products, NADPH and ribose, attenuated aescin-induced apoptosis. Furthermore, aescin-induced ROS elevation and autophagy activation were further strengthened by TIGAR knockdown in HCT-116 cells. However, autophagy inhibition by knockdown of autophagy-related gene ATG5 or 3-methyladenine (3-MA) exaggerated aescin-induced apoptosis when TIGAR was knocked down. In conclusion, TIGAR plays a ...Continue Reading

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Citations

Nov 20, 2018·Frontiers in Oncology·Weifen ZhangWentong Li
Feb 5, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Bing Han, Chengwei He
Jul 1, 2020·Recent Patents on Anti-cancer Drug Discovery·Javad Saffari-ChaleshtoriSayed Mohammad Shafiee
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Avez SharipovJamoliddin Razzokov

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Methods Mentioned

BETA
xenograft
flow cytometry
confocal microscopy
fluorescence microscopy

Software Mentioned

GraphPad
GraphPad Prism
Cell Quest Pro

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