Berberine Suppresses Cyclin D1 Expression through Proteasomal Degradation in Human Hepatoma Cells

Ning Wang; Xuanbin Wang; Hor-Yue Tan; Sha Li; Chi Man Tsang; Sai-Wah Tsao; Yibin Feng

doi:10.3390/ijms17111899

Berberine Suppresses Cyclin D1 Expression through Proteasomal Degradation in Human Hepatoma Cells

Ning Wang, Xuanbin Wang, Hor-Yue Tan, Sha Li, Chi Man Tsang, Sai-Wah Tsao, Yibin Feng^*

^*Corresponding author for this work

Centre for Chinese Herbal Medicine Drug Development Limited

Research output: Contribution to journal › Journal article › peer-review

43 Citations (Scopus)

Abstract

The aim of this study is to explore the underlying mechanism on berberine-induced Cyclin D1 degradation in human hepatic carcinoma. We observed that berberine could suppress both in vitro and in vivo expression of Cyclin D1 in hepatoma cells. Berberine exhibits dose- and time-dependent inhibition on Cyclin D1 expression in human hepatoma cell HepG2. Berberine increases the phosphorylation of Cyclin D1 at Thr286 site and potentiates Cyclin D1 nuclear export to cytoplasm for proteasomal degradation. In addition, berberine recruits the Skp, Cullin, F-box containing complex-β-Transducin Repeat Containing Protein (SCFβ^-TrCP) complex to facilitate Cyclin D1 ubiquitin-proteasome dependent proteolysis. Knockdown of β-TrCP blocks Cyclin D1 turnover induced by berberine; blocking the protein degradation induced by berberine in HepG2 cells increases tumor cell resistance to berberine. Our results shed light on berberine′ s potential as an anti-tumor agent for clinical cancer therapy.

Original language	English
Article number	1899
Number of pages	13
Journal	International Journal of Molecular Sciences
Volume	17
Issue number	11
DOIs	https://doi.org/10.3390/ijms17111899
Publication status	Published - 15 Nov 2016

Scopus Subject Areas

Catalysis
Molecular Biology
Spectroscopy
Computer Science Applications
Physical and Theoretical Chemistry
Organic Chemistry
Inorganic Chemistry

User-Defined Keywords

Berberine
Cyclin D1
Ubiquitinated-dependent proteolysis
β-TrCP
tumor growth inhibition

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/ijms17111899

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title = "Berberine Suppresses Cyclin D1 Expression through Proteasomal Degradation in Human Hepatoma Cells",

abstract = "The aim of this study is to explore the underlying mechanism on berberine-induced Cyclin D1 degradation in human hepatic carcinoma. We observed that berberine could suppress both in vitro and in vivo expression of Cyclin D1 in hepatoma cells. Berberine exhibits dose- and time-dependent inhibition on Cyclin D1 expression in human hepatoma cell HepG2. Berberine increases the phosphorylation of Cyclin D1 at Thr286 site and potentiates Cyclin D1 nuclear export to cytoplasm for proteasomal degradation. In addition, berberine recruits the Skp, Cullin, F-box containing complex-β-Transducin Repeat Containing Protein (SCFβ-TrCP) complex to facilitate Cyclin D1 ubiquitin-proteasome dependent proteolysis. Knockdown of β-TrCP blocks Cyclin D1 turnover induced by berberine; blocking the protein degradation induced by berberine in HepG2 cells increases tumor cell resistance to berberine. Our results shed light on berberine′ s potential as an anti-tumor agent for clinical cancer therapy.",

keywords = "Berberine, Cyclin D1, Ubiquitinated-dependent proteolysis, β-TrCP, tumor growth inhibition",

author = "Ning Wang and Xuanbin Wang and Hor-Yue Tan and Sha Li and Tsang, {Chi Man} and Sai-Wah Tsao and Yibin Feng",

note = "Funding Information: The study was financially supported by grants from the research council of the University of Hong Kong (Project Codes: 104001764, 10400699, 104002320, 104002889, 104003422), Wong0s Donation on Modern Oncology of Chinese Medicine (Project code: 200006276), Gala Family Trust (Project Code: 200007008), Government-Matching Grant Scheme (Project Code: 207060411), National Natural Science Foundation of China (Project Code: 81302808), the Open Project of Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine (Grant No. WDCM001), the Young Scientist Innovation Team Project of Hubei Colleges (Grant No.T201510) and the Research Grant Committee (RGC) of Hong Kong SAR of China (RGC General Research Fund, Project Code: 766211). The authors would like to express thanks to Keith Wong, Cindy Lee, Alex Shek, and the Faculty Core Facility for their technical support. Publisher Copyright: {\textcopyright} 2016 by the authors; licensee MDPI, Basel, Switzerland.",

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AU - Wang, Ning

AU - Wang, Xuanbin

AU - Tan, Hor-Yue

AU - Li, Sha

AU - Tsang, Chi Man

AU - Tsao, Sai-Wah

AU - Feng, Yibin

N1 - Funding Information: The study was financially supported by grants from the research council of the University of Hong Kong (Project Codes: 104001764, 10400699, 104002320, 104002889, 104003422), Wong0s Donation on Modern Oncology of Chinese Medicine (Project code: 200006276), Gala Family Trust (Project Code: 200007008), Government-Matching Grant Scheme (Project Code: 207060411), National Natural Science Foundation of China (Project Code: 81302808), the Open Project of Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine (Grant No. WDCM001), the Young Scientist Innovation Team Project of Hubei Colleges (Grant No.T201510) and the Research Grant Committee (RGC) of Hong Kong SAR of China (RGC General Research Fund, Project Code: 766211). The authors would like to express thanks to Keith Wong, Cindy Lee, Alex Shek, and the Faculty Core Facility for their technical support. Publisher Copyright: © 2016 by the authors; licensee MDPI, Basel, Switzerland.

PY - 2016/11/15

Y1 - 2016/11/15

N2 - The aim of this study is to explore the underlying mechanism on berberine-induced Cyclin D1 degradation in human hepatic carcinoma. We observed that berberine could suppress both in vitro and in vivo expression of Cyclin D1 in hepatoma cells. Berberine exhibits dose- and time-dependent inhibition on Cyclin D1 expression in human hepatoma cell HepG2. Berberine increases the phosphorylation of Cyclin D1 at Thr286 site and potentiates Cyclin D1 nuclear export to cytoplasm for proteasomal degradation. In addition, berberine recruits the Skp, Cullin, F-box containing complex-β-Transducin Repeat Containing Protein (SCFβ-TrCP) complex to facilitate Cyclin D1 ubiquitin-proteasome dependent proteolysis. Knockdown of β-TrCP blocks Cyclin D1 turnover induced by berberine; blocking the protein degradation induced by berberine in HepG2 cells increases tumor cell resistance to berberine. Our results shed light on berberine′ s potential as an anti-tumor agent for clinical cancer therapy.

AB - The aim of this study is to explore the underlying mechanism on berberine-induced Cyclin D1 degradation in human hepatic carcinoma. We observed that berberine could suppress both in vitro and in vivo expression of Cyclin D1 in hepatoma cells. Berberine exhibits dose- and time-dependent inhibition on Cyclin D1 expression in human hepatoma cell HepG2. Berberine increases the phosphorylation of Cyclin D1 at Thr286 site and potentiates Cyclin D1 nuclear export to cytoplasm for proteasomal degradation. In addition, berberine recruits the Skp, Cullin, F-box containing complex-β-Transducin Repeat Containing Protein (SCFβ-TrCP) complex to facilitate Cyclin D1 ubiquitin-proteasome dependent proteolysis. Knockdown of β-TrCP blocks Cyclin D1 turnover induced by berberine; blocking the protein degradation induced by berberine in HepG2 cells increases tumor cell resistance to berberine. Our results shed light on berberine′ s potential as an anti-tumor agent for clinical cancer therapy.

KW - Berberine

KW - Cyclin D1

KW - Ubiquitinated-dependent proteolysis

KW - β-TrCP

KW - tumor growth inhibition

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DO - 10.3390/ijms17111899

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SN - 1661-6596

VL - 17

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

IS - 11

M1 - 1899

ER -

Berberine Suppresses Cyclin D1 Expression through Proteasomal Degradation in Human Hepatoma Cells

Abstract

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