Evodiamine inhibits migration and invasion by Sirt1-mediated post-translational modulations in colorectal cancer

Anti-cancer Drugs
Peng ZhouDi-Long Chen

Abstract

Colorectal cancer (CRC) is one of the most difficult cancers to cure. An important prognostic factor is metastasis, which precludes curative surgical resection. Recent evidences show that Evodiamine (EVO) exerts an inhibitory effect on cancer cell apoptosis, migration, and invasion. In this study, we investigated the effects of EVO on the metastasis of CRC cells in vitro and in vivo. In vitro, wound-healing and transwell assay showed that migration and invasion of HT-29 and HCT-116 CRC cells were inhibited significantly by EVO. Western blot and RT-PCR showed that EVO reduced the expression of matrix metalloproteinase-9 in a dose-dependent manner. In EVO-induced cells, the intracellular NAD+/NADH ratio was increased, the level of Sirt1 was increased, and acetyl-NF-κB P65 was decreased. This process was inhibited by nicotinamide, an inhibitor of Sirt1. In vivo, EVO reduced tumor metastasis markedly. These findings provide evidences that EVO suppresses the migration and invasion of CRC cells by inhibiting the acetyl-NF-κB p65 by Sirt1, resulting in suppression of metalloproteinase-9 expression in vitro and in vivo.

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Citations

Jul 31, 2019·Naunyn-Schmiedeberg's Archives of Pharmacology·Hanzhang ZhuChangku Jia
Dec 15, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hyejin KimWoo-Young Kim
Dec 31, 2019·Seminars in Cancer Biology·Thomas Efferth, Franz Oesch

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Methods Mentioned

BETA
PCR
Protein Assay
Fluorescence
Assay
acetylation

Software Mentioned

SPSS

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