title: Berberine suppresses the TPA-induced MMP-1 and MMP-9 expressions through the inhibition of PKC-α in breast cancer cells.
abstract: BACKGROUND
  Berberine (BBR) is one of the major alkaloids, and it has been reported to have a variety of pharmacologic effects, including inhibition of cell cycle progression. Here, we investigated the effect of BBR on the MMP-1 and MMP-9 expressions, which are predictors of metastasis and invasion in breast cancer cells.
  
  
  METHODS
  MMP-1 and MMP-9 mRNA expressions were analyzed by real-time PCR. The levels of MMP-1 protein and PKC-α phosphorylation were detected by Western blotting. MMP-9 protein expression was detected by gelatin zymography. Cell cycle was analyzed by FACS analysis. PKC-α knock-down was examined by PKC-α siRNA transfection.
  
  
  RESULTS
  The basal levels of both the MMP-1 and MMP-9 mRNA expressions were decreased by BBR treatment in a dose-dependent manner. In contrast, TPA, which is a tumor promoter, significantly increased the levels of the MMP-1 and MMP-9 mRNA and protein expressions in the MCF-7 breast cancer cells. We also observed that the TPA-induced MMP-1 and MMP-9 mRNA and protein expressions were prevented by BBR treatment. In addition, the TPA-induced MMP-1 and MMP-9 expressions were completely decreased by Go6983 and PKC-α siRNA, respectively. TPA-induced PKC-α phosphorylation was dose-dependently decreased by BBR treatment.
  
  
  CONCLUSIONS
  The TPA-induced PKC-α phosphorylation is suppressed and then the MMP-1 and MMP-9 expressions are also inhibited by berberine. Therefore, we suggest that berberine may be used as a candidate drug for the inhibition of metastasis of human breast cancer.
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-Gu, Seoul, South Korea.
authors.forename: Sangmin
authors.initials: S
authors.lastname: Kim
authors.forename: Jeonghun
authors.initials: J
authors.lastname: Han
authors.forename: Se Kyung
authors.initials: SK
authors.lastname: Lee
authors.forename: Min-Young
authors.initials: MY
authors.lastname: Choi
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Kim
authors.forename: Jeonghui
authors.initials: J
authors.lastname: Lee
authors.forename: Seung Pil
authors.initials: SP
authors.lastname: Jung
authors.forename: Jee Soo
authors.initials: JS
authors.lastname: Kim
authors.forename: Jung-Han
authors.initials: JH
authors.lastname: Kim
authors.forename: Jun-Ho
authors.initials: JH
authors.lastname: Choe
authors.forename: Jeong Eon
authors.initials: JE
authors.lastname: Lee
authors.forename: Seok Jin
authors.initials: SJ
authors.lastname: Nam
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D001599:Berberine / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002273:Carcinogens / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051571:Protein Kinase C-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
chemical_list: D002273:Carcinogens; D012333:RNA, Messenger; D001599:Berberine; C496628:PRKCA protein, human; D051571:Protein Kinase C-alpha; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1; D013755:Tetradecanoylphorbol Acetate