title: Berberine suppresses TPA-induced fibronectin expression through the inhibition of VEGF secretion in breast cancer cells.
abstract: OBJECTIVE
  Berberine (BBR) is an isoquinoline alkaloid and is beneficial for the anticancer effect on a variety of human tumor cells. However, BBR's anti-angiogenesis property and its clinical potential as an inhibitor of tumor angiogenesis in breast cancer cells have not been fully elucidated. Here, we investigated the effect of BBR on TPA-induced VEGF and fibronectin (FN) as well as VEGF-induced FN in breast cancer cells.
  
  
  METHODS
  The secretion of VEGF protein was detected by ELISA. Fibronectin mRNA and protein expression was analyzed by Real-Time PCR and western blotting, respectively. The overexpressions of CA-MEK, and CA-Akt were examined by adenovirus system.
  
  
  RESULTS
  Our results showed that TPA, a tumor promoter, significantly increased the level of VEGF and FN expression in both MCF7 and T47D breast cancer cells. On the other hand, TPA-induced VEGF and FN expression was suppressed by LY294002, a PI-3K inhibitor. In contrast, the level of FN expression also significantly increased by constitutively active (CA)-AKT overexpression. We also found that TPA-induced VEGF and FN expression was decreased by BBR treatment. Finally, our results showed that VEGF augmented the expression of FN whereas VEGF-induced FN expression was decreased by BBR treatment.
  
  
  CONCLUSIONS
  Taken together, we suggest that BBR may suppress TPA-induced VEGF and FN as well as VEGF-induced FN through the inhibition of the PI-3K/AKT pathway in breast cancer cells. Therefore, we suggest that BBR may be used as a candidate drug for the inhibition of angiogenesis of human breast cancer.
authors: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors: Sangmin
authors: S
authors: Kim
authors: Soo-Jin
authors: SJ
authors: Oh
authors: Jeongmin
authors: J
authors: Lee
authors: Jeonghun
authors: J
authors: Han
authors: Myeongjin
authors: M
authors: Jeon
authors: Taewoo
authors: T
authors: Jung
authors: Se Kyung
authors: SK
authors: Lee
authors: Soo Youn
authors: SY
authors: Bae
authors: Jiyoung
authors: J
authors: Kim
authors: Won Ho
authors: WH
authors: Gil
authors: Seok Won
authors: SW
authors: Kim
authors: Jeong Eon
authors: JE
authors: Lee
authors: Seok Jin
authors: SJ
authors: Nam
mesh_terms: D001599:Berberine / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D005353:Fibronectins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D001599:Berberine; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D013755:Tetradecanoylphorbol Acetate