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01-06-2019 | Original Article

Ponicidin inhibits pro-inflammatory cytokine TNF-α-induced epithelial–mesenchymal transition and metastasis of colorectal cancer cells via suppressing the AKT/GSK-3β/Snail pathway

Authors: Zhengguang Zhang, Jingjing Xu, Bing Liu, Feiyan Chen, Jiao Li, Yuchen Liu, Jiapeng Zhu, Cunsi Shen

Published in: Inflammopharmacology | Issue 3/2019

Abstract

Ponicidin (PON), a natural diterpenoid compound, has been shown to exhibit potent anticancer activities in a wide variety of cancers, including colorectal cancer (CRC). Nevertheless, the precise mechanisms underlying the anti-metastasis effect of PON have not yet been completely defined. The present study was designed to uncover the inhibitory effect of PON on epithelial–mesenchymal transition (EMT), migration and invasion of HCT116 cells induced by pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) in vitro, and liver metastasis in vivo. Briefly, cell proliferation was assessed by Cell Counting Kit-8 assay, followed by wound healing and transwell assays to evaluate cell migration and invasion. The EMT-related molecular markers were determined through quantitative real-time polymerase chain reaction (qPCR), immunofluorescence (IF), western blot (WB), and immunohistochemistry (IHC). Additionally, WB was used to assess the expression of AKT, phosphorylated AKT (p-AKT), GSK-3β, and phosphorylated GSK-3β (p-GSK-3β). As a result, PON could effectively suppress EMT, migration, and invasion in HCT116 cells in vitro, and liver metastasis of HCT116 cells in vivo. Additionally, PON administration also dramatically altered the expression of EMT-associated markers such as E-cadherin, N-cadherin, and Vimentin, and suppressed the expression of p-AKT, p-GSK-3β and transcription factor, Snail in a dose-dependent manner. Moreover, the incidence of liver metastasis in the control group was 100% and although the incidence of liver metastasis did not decrease, the number of metastatic nodules in the livers of each PON dose group decreased by (34 ± 4.2)%, (64 ± 3.6)%, and (76 ± 5.3)%, respectively, compared to the control group. Collectively, these findings indicated that targeting the AKT/GSK-3β/Snail pathway by PON might be a promising treatment for TNF-α-induced EMT and metastasis of CRC.

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Title: Ponicidin inhibits pro-inflammatory cytokine TNF-α-induced epithelial–mesenchymal transition and metastasis of colorectal cancer cells via suppressing the AKT/GSK-3β/Snail pathway
Authors: Zhengguang Zhang
Jingjing Xu
Bing Liu
Feiyan Chen
Jiao Li
Yuchen Liu
Jiapeng Zhu
Cunsi Shen
Publication date: 01-06-2019
Publisher: Springer International Publishing
Published in: Inflammopharmacology / Issue 3/2019
Print ISSN: 0925-4692
Electronic ISSN: 1568-5608
DOI: https://doi.org/10.1007/s10787-018-0534-5

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Ponicidin inhibits pro-inflammatory cytokine TNF-α-induced epithelial–mesenchymal transition and metastasis of colorectal cancer cells via suppressing the AKT/GSK-3β/Snail pathway

Abstract

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

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