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

Research output: Contribution to journalJournal articlepeer-review

46 Citations (Scopus)


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 languageEnglish
Article number1899
Number of pages13
JournalInternational Journal of Molecular Sciences
Issue number11
Publication statusPublished - 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


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