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.
authors.affiliation: School of Chinese Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong, China. ckwang@hku.hk.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: Laboratory of Chinese Herbal Pharmacology, Oncology Center, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, China. wangxb@hbmu.edu.cn.|Hubei Key Laboratory of Wudang Local Chinese Medicine Research and School of Pharmacy, Hubei University of Medicine, Shiyan 442000, China. wangxb@hbmu.edu.cn.
authors.forename: Xuanbin
authors.initials: X
authors.lastname: Wang
authors.affiliation: School of Chinese Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong, China. hoeytan@hku.hk.
authors.forename: Hor-Yue
authors.initials: HY
authors.lastname: Tan
authors.affiliation: School of Chinese Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong, China. u3003781@connect.hku.hk.
authors.forename: Sha
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Anatomy, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, China. annatsan@hku.hk.
authors.forename: Chi Man
authors.initials: CM
authors.lastname: Tsang
authors.affiliation: Department of Anatomy, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, China. gswtsao@hku.hk.
authors.forename: Sai-Wah
authors.initials: SW
authors.lastname: Tsao
authors.affiliation: School of Chinese Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong, China. yfeng@hku.hk.|Laboratory of Chinese Herbal Pharmacology, Oncology Center, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, China. yfeng@hku.hk.|Hubei Key Laboratory of Wudang Local Chinese Medicine Research and School of Pharmacy, Hubei University of Medicine, Shiyan 442000, China. yfeng@hku.hk.
authors.forename: Yibin
authors.initials: Y
authors.lastname: Feng
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001599:Berberine / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019938:Cyclin D1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects* / Q000378:metabolism; D059748:Proteolysis / Q000187:drug effects; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D044844:beta-Transducin Repeat-Containing Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D034741:RNA, Small Interfering; D025801:Ubiquitin; D044844:beta-Transducin Repeat-Containing Proteins; D001599:Berberine; D019938:Cyclin D1; D046988:Proteasome Endopeptidase Complex
keywords: Cyclin D1; berberine; tumor growth inhibition; ubiquitinated-dependent proteolysis; β-TrCP