Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 17, Issue 11, Pages -Publisher
MDPI
DOI: 10.3390/ijms17111899
Keywords
berberine; Cyclin D1; ubiquitinated-dependent proteolysis; beta-TrCP; tumor growth inhibition
Funding
- research council of the University of Hong Kong [104001764, 10400699, 104002320, 104002889, 104003422]
- Wong's Donation on Modern Oncology of Chinese Medicine [200006276]
- Gala Family Trust [200007008]
- Government-Matching Grant Scheme [207060411]
- National Natural Science Foundation of China [81302808]
- Open Project of Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine [WDCM001]
- Young Scientist Innovation Team Project of Hubei Colleges [T201510]
- Research Grant Committee (RGC) of Hong Kong SAR of China (RGC General Research Fund) [766211]
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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-beta-Transducin Repeat Containing Protein (SCF beta-TrCP) complex to facilitate Cyclin D1 ubiquitin-proteasome dependent proteolysis. Knockdown of beta-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.
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