Rhubarb inhibits hepatocellular carcinoma cell metastasis via GSK-3-β activation to enhance protein degradation and attenuate nuclear translocation of β-catenin

Kun Hsi Tsai; Hau Hsueh Hsien; Li Mien Chen; Wei Jen Ting; Yuh-Shyong Yang; Chia Hua Kuo; Chang Hai Tsai; Fuu Jen Tsai; Henry J. Tsai; Chih Yang Huang

doi:10.1016/j.foodchem.2012.10.038

Rhubarb inhibits hepatocellular carcinoma cell metastasis via GSK-3-β activation to enhance protein degradation and attenuate nuclear translocation of β-catenin

Kun Hsi Tsai, Hau Hsueh Hsien, Li Mien Chen, Wei Jen Ting, Yuh-Shyong Yang, Chia Hua Kuo, Chang Hai Tsai, Fuu Jen Tsai, Henry J. Tsai, Chih Yang Huang^*

^*Corresponding author for this work

Department of Biological Science and Technology

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

Abstract

The aim of our study was to investigate the mechanisms by which rhubarb regulates β-catenin as well as metastasis of hepatocellular carcinomas. Our results revealed that rhubarb extract inhibited HA22T cell migration ability in wound healing, migration and invasion assays in a dose-dependent manner. Rhubarb also reduced β-catenin protein level, downregulated its downstream proteins, cyclin D, Tbx3 and c-Myc, and attenuated the expression of MMP9 and contactin-1 metastatic factors. Additionally, rhubarb inhibited β-catenin nuclear accumulation and induced its degradation via proteasome-mediated pathway. Furthermore, we found that rhubarb suppressed the p-ser⁹ GSK-3-β protein level to inactivate Wnt signalling and reduce β-catenin protein level. Taken together; we found that rhubarb blocked the metastatic process of HA22T hepatocellular carcinoma cells mediated through GSK-3-β activation, and enhancement of protein degradation as well as reduction of the nuclear accumulation of β-catenin.

Original language	English
Pages (from-to)	278-285
Number of pages	8
Journal	Food Chemistry
Volume	138
Issue number	1
DOIs	https://doi.org/10.1016/j.foodchem.2012.10.038
State	Published - 1 May 2013

Keywords

GSK-3-β
Hepatocellular carcinoma (HCC)
Rhubarb
β-Catenin

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Tsai, K. H., Hsien, H. H., Chen, L. M., Ting, W. J., Yang, Y.-S., Kuo, C. H., Tsai, C. H., Tsai, F. J., Tsai, H. J., & Huang, C. Y. (2013). Rhubarb inhibits hepatocellular carcinoma cell metastasis via GSK-3-β activation to enhance protein degradation and attenuate nuclear translocation of β-catenin. Food Chemistry, 138(1), 278-285. https://doi.org/10.1016/j.foodchem.2012.10.038

@article{da884c2be938457f97876c1d3a4e2a2e,

title = "Rhubarb inhibits hepatocellular carcinoma cell metastasis via GSK-3-β activation to enhance protein degradation and attenuate nuclear translocation of β-catenin",

abstract = "The aim of our study was to investigate the mechanisms by which rhubarb regulates β-catenin as well as metastasis of hepatocellular carcinomas. Our results revealed that rhubarb extract inhibited HA22T cell migration ability in wound healing, migration and invasion assays in a dose-dependent manner. Rhubarb also reduced β-catenin protein level, downregulated its downstream proteins, cyclin D, Tbx3 and c-Myc, and attenuated the expression of MMP9 and contactin-1 metastatic factors. Additionally, rhubarb inhibited β-catenin nuclear accumulation and induced its degradation via proteasome-mediated pathway. Furthermore, we found that rhubarb suppressed the p-ser9 GSK-3-β protein level to inactivate Wnt signalling and reduce β-catenin protein level. Taken together; we found that rhubarb blocked the metastatic process of HA22T hepatocellular carcinoma cells mediated through GSK-3-β activation, and enhancement of protein degradation as well as reduction of the nuclear accumulation of β-catenin.",

keywords = "GSK-3-β, Hepatocellular carcinoma (HCC), Rhubarb, β-Catenin",

author = "Tsai, {Kun Hsi} and Hsien, {Hau Hsueh} and Chen, {Li Mien} and Ting, {Wei Jen} and Yuh-Shyong Yang and Kuo, {Chia Hua} and Tsai, {Chang Hai} and Tsai, {Fuu Jen} and Tsai, {Henry J.} and Huang, {Chih Yang}",

year = "2013",

month = may,

day = "1",

doi = "10.1016/j.foodchem.2012.10.038",

language = "English",

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journal = "Food Chemistry",

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T1 - Rhubarb inhibits hepatocellular carcinoma cell metastasis via GSK-3-β activation to enhance protein degradation and attenuate nuclear translocation of β-catenin

AU - Tsai, Kun Hsi

AU - Hsien, Hau Hsueh

AU - Chen, Li Mien

AU - Ting, Wei Jen

AU - Yang, Yuh-Shyong

AU - Kuo, Chia Hua

AU - Tsai, Chang Hai

AU - Tsai, Fuu Jen

AU - Tsai, Henry J.

AU - Huang, Chih Yang

PY - 2013/5/1

Y1 - 2013/5/1

N2 - The aim of our study was to investigate the mechanisms by which rhubarb regulates β-catenin as well as metastasis of hepatocellular carcinomas. Our results revealed that rhubarb extract inhibited HA22T cell migration ability in wound healing, migration and invasion assays in a dose-dependent manner. Rhubarb also reduced β-catenin protein level, downregulated its downstream proteins, cyclin D, Tbx3 and c-Myc, and attenuated the expression of MMP9 and contactin-1 metastatic factors. Additionally, rhubarb inhibited β-catenin nuclear accumulation and induced its degradation via proteasome-mediated pathway. Furthermore, we found that rhubarb suppressed the p-ser9 GSK-3-β protein level to inactivate Wnt signalling and reduce β-catenin protein level. Taken together; we found that rhubarb blocked the metastatic process of HA22T hepatocellular carcinoma cells mediated through GSK-3-β activation, and enhancement of protein degradation as well as reduction of the nuclear accumulation of β-catenin.

AB - The aim of our study was to investigate the mechanisms by which rhubarb regulates β-catenin as well as metastasis of hepatocellular carcinomas. Our results revealed that rhubarb extract inhibited HA22T cell migration ability in wound healing, migration and invasion assays in a dose-dependent manner. Rhubarb also reduced β-catenin protein level, downregulated its downstream proteins, cyclin D, Tbx3 and c-Myc, and attenuated the expression of MMP9 and contactin-1 metastatic factors. Additionally, rhubarb inhibited β-catenin nuclear accumulation and induced its degradation via proteasome-mediated pathway. Furthermore, we found that rhubarb suppressed the p-ser9 GSK-3-β protein level to inactivate Wnt signalling and reduce β-catenin protein level. Taken together; we found that rhubarb blocked the metastatic process of HA22T hepatocellular carcinoma cells mediated through GSK-3-β activation, and enhancement of protein degradation as well as reduction of the nuclear accumulation of β-catenin.

KW - GSK-3-β

KW - Hepatocellular carcinoma (HCC)

KW - Rhubarb

KW - β-Catenin

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DO - 10.1016/j.foodchem.2012.10.038

M3 - Article

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AN - SCOPUS:84870199455

SN - 0308-8146

VL - 138

SP - 278

EP - 285

JO - Food Chemistry

JF - Food Chemistry

IS - 1

ER -

Rhubarb inhibits hepatocellular carcinoma cell metastasis via GSK-3-β activation to enhance protein degradation and attenuate nuclear translocation of β-catenin

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Keywords

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