title: Berberine, an isoquinoline alkaloid, inhibits the metastatic potential of breast cancer cells via Akt pathway modulation.
abstract: Berberine (BBR) is a natural alkaloid with significant antitumor activities against many types of cancer cells. In this study, we investigated the molecular mechanisms by which BBR repressed the metastatic potential of breast cancer cells. BBR was found to downregulate the enzymatic activities and expression levels of matrix metalloproteinases 2 and 9 (MMP2 and MMP9, respectively). The BBR-mediated suppression of MMP2 and MMP9 involved the inhibition of the Akt/nuclear factor kappa B (NF-κB) and activator protein-1 (AP-1) signaling pathways. Furthermore, BBR repressed the expression of the Akt protein by modulating the mRNA expression level and protein degradation of Akt. In conclusion, this study suggests that BBR can reduce the metastatic potential of highly metastatic breast cancer cells and may be a useful adjuvant therapeutic agent in the treatment of breast cancer by targeting the Akt pathway.
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung, Taiwan.
authors.forename: Han-Peng
authors.initials: HP
authors.lastname: Kuo
authors.forename: Tzu-Chao
authors.initials: TC
authors.lastname: Chuang
authors.forename: Shih-Chang
authors.initials: SC
authors.lastname: Tsai
authors.forename: Hsiu-Hsueh
authors.initials: HH
authors.lastname: Tseng
authors.forename: Shih-Chung
authors.initials: SC
authors.lastname: Hsu
authors.forename: Yu-Chang
authors.initials: YC
authors.lastname: Chen
authors.forename: Chao-Lin
authors.initials: CL
authors.lastname: Kuo
authors.forename: Yueh-Hsiung
authors.initials: YH
authors.lastname: Kuo
authors.forename: Jah-Yao
authors.initials: JY
authors.lastname: Liu
authors.forename: Ming-Ching
authors.initials: MC
authors.lastname: Kao
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001599:Berberine / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D061986:MCF-7 Cells / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D001599:Berberine; D051057:Proto-Oncogene Proteins c-akt; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9