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Int. J. Mol. Sci. 2016, 17(11), 1899; doi:10.3390/ijms17111899

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

1
School of Chinese Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong, China
2
Laboratory of Chinese Herbal Pharmacology, Oncology Center, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, China
3
Hubei Key Laboratory of Wudang Local Chinese Medicine Research and School of Pharmacy, Hubei University of Medicine, Shiyan 442000, China
4
Department of Anatomy, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, China
*
Author to whom correspondence should be addressed.
Academic Editor: Toshio Morikawa
Received: 27 September 2016 / Revised: 4 November 2016 / Accepted: 9 November 2016 / Published: 15 November 2016
(This article belongs to the Special Issue Biological Activity of Natural Secondary Metabolite Products)
View Full-Text   |   Download PDF [3873 KB, uploaded 15 November 2016]   |  

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. View Full-Text
Keywords: berberine; Cyclin D1; ubiquitinated-dependent proteolysis; β-TrCP; tumor growth inhibition berberine; Cyclin D1; ubiquitinated-dependent proteolysis; β-TrCP; tumor growth inhibition
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Wang, N.; Wang, X.; Tan, H.-Y.; Li, S.; Tsang, C.M.; Tsao, S.-W.; Feng, Y. Berberine Suppresses Cyclin D1 Expression through Proteasomal Degradation in Human Hepatoma Cells. Int. J. Mol. Sci. 2016, 17, 1899.

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