title: Berberine inhibits the metastatic ability of prostate cancer cells by suppressing epithelial-to-mesenchymal transition (EMT)-associated genes with predictive and prognostic relevance.
abstract: BACKGROUND
  Over 70% of cancer metastasis from prostate cancer develops bone metastases that are not sensitive to hormonal therapy, radiation therapy, or chemotherapy. The epithelial-to-mesenchymal transition (EMT) genetic program is implicated as a significant contributor to prostate cancer progression. As such, targeting the EMT represents an important therapeutic strategy for preventing or treating prostate cancer metastasis. Berberine is a natural alkaloid with significant antitumor activities against many types of cancer cells. In this study, we investigated the molecular mechanism by which berberine represses the metastatic potential of prostate cancer.
  
  
  METHODS
  The effects of berberine on cell migration and invasion were determined by transwell migration assay and Matrigel invasion assay. Expressions of EMT-related genes were determined by an EMT PCR Array and a quantitative RT-PCR. The prognostic relevance of berberine's modulation of EMT-related genes in prostate cancer was evaluated using Kaplan-Meier survival analysis.
  
  
  RESULTS
  Berberine exerted inhibitory effects on the migratory and invasive abilities of highly metastatic prostate cancer cells. These inhibitory effects of berberine resulted in significant repression of a panel of mesenchymal genes that regulate the developmental EMT. Among EMT-related genes downregulated by berberine, high BMP7, NODAL and Snail gene expressions of metastatic prostate cancer tissues were associated with shorter survival of prostate cancer patients and provide potential therapeutic interventions.
  
  
  CONCLUSIONS
  We concluded that berberine should be developed as a pharmacological agent for use in combination with other anticancer drug for treating metastatic prostate cancer.
authors.affiliation: 1. Department of Urology, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan;
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Liu
authors.affiliation: 2. Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan;
authors.forename: Wan-Chun
authors.initials: WC
authors.lastname: Tang
authors.affiliation: 2. Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan;
authors.forename: Peik
authors.initials: P
authors.lastname: Sia
authors.affiliation: 3. The PhD Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan;
authors.forename: Chi-Chen
authors.initials: CC
authors.lastname: Huang
authors.affiliation: 2. Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan;
authors.forename: Pei-Ming
authors.initials: PM
authors.lastname: Yang
authors.affiliation: 4. The PhD Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ming-Heng
authors.initials: MH
authors.lastname: Wu
authors.affiliation: 5. Division of Medicinal Chemistry, College of Pharmacy and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors.forename: I-Lu
authors.initials: IL
authors.lastname: Lai
authors.affiliation: 2. Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan;
authors.forename: Kuen-Haur
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology; D001599:Berberine / Q000008:administration & dosage / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000235:genetics; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D055457:Nodal Protein / Q000235:genetics; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D051153:Wnt Proteins / Q000235:genetics
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C525819:BMP7 protein, human; D014408:Biomarkers, Tumor; D055419:Bone Morphogenetic Protein 7; C526007:NODAL protein, human; D055457:Nodal Protein; D051153:Wnt Proteins; C540523:Wnt11 protein, human; D001599:Berberine
keywords: Berberine; EMT; Prostate cancer.