@article{4d515f46d776433d94c638be7e2619d4,
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.",
year = "2016",
month = nov,
day = "15",
doi = "10.3390/ijms17111899",
language = "English",
volume = "17",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "MDPI",
number = "11",
}
