title: Nelumbo nucifera Gaertn leaves extract inhibits the angiogenesis and metastasis of breast cancer cells by downregulation connective tissue growth factor (CTGF) mediated PI3K/AKT/ERK signaling.
abstract: BACKGROUND
  Nelumbo nucifera Gaertn (Nymphaeaceae) has been recognized as a medicinal plant, which was distributed throughout the Asia. The aqueous extract of Nelumbo nucifera leaves extract (NLE) has various biologically active components such as polyphenols, flavonoids, oligomeric procyanidines. However, the role of NLE in breast cancer therapy is poorly understood.
  
  
  OBJECTIVE
  The purpose of this study was to identify the hypothesis that NLE can suppress tumor angiogenesis and metastasis through CTGF (connective tissue growth factor), which has been implicated in tumor angiogenesis and progression in breast cancer MDA-MB-231 cells.
  
  
  RESULTS
  We examined the effects of NLE on angiogenesis in the chicken chorioallantoic membrane (CAM) model. The data showed that NLE could reduce the chorionic plexus at day 17 in CAM and the duration of this inhibition was dose-dependent. In Xenograft model, NLE treatment significantly reduced tumor weight and CD31 (capillary density) over control, respectively. We examined the role of angiogenesis involved restructuring of endothelium using human umbilical vein endothelial cell (HUVEC) in Matrigel angiogenesis model. The results indicated that vascular-like structure formation was further blocked by NLE treatment. Moreover, knockdown of CTGF expression markedly reduced the expression of MMP2 as well as VEGF, and attenuated PI3K-AKT-ERK activation, indication that these signaling pathways are crucial in mediating CTGF function.
  
  
  CONCLUSIONS
  The present results suggest that NLE might be useful for treatment in therapy-resistance triple negative breast cancer.
authors.affiliation: Institute of Biochemistry, Microbiology and Immunology, Chung-Shan Medical University, No. 110, Section 1, Jiankuo North Road, Taichung 40201, Taiwan.
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Chang
authors.affiliation: Institute of Biochemistry, Microbiology and Immunology, Chung-Shan Medical University, No. 110, Section 1, Jiankuo North Road, Taichung 40201, Taiwan.
authors.forename: Ting-Tsz
authors.initials: TT
authors.lastname: Ou
authors.affiliation: Institute of Biochemistry, Microbiology and Immunology, Chung-Shan Medical University, No. 110, Section 1, Jiankuo North Road, Taichung 40201, Taiwan.
authors.forename: Mon-Yuan
authors.initials: MY
authors.lastname: Yang
authors.affiliation: School of Medicine, Chung Shan Medical University, No. 110, Section 1, Jiankuo North Road, Taichung 40201, Taiwan; Department of Surgery, Division of Colon and Rectum, Chung Shan Medical University Hospital, No. 110, Sec. 1, Jianguo N. Road, Taichung 40201, Taiwan.
authors.forename: Chi-Chou
authors.initials: CC
authors.lastname: Huang
authors.affiliation: Institute of Biochemistry, Microbiology and Immunology, Chung-Shan Medical University, No. 110, Section 1, Jiankuo North Road, Taichung 40201, Taiwan; Department of Medical Research, Chung Shan Medical University Hospital, No. 110, Sec. 1, Jianguo N. Road, Taichung 40201, Taiwan. Electronic address: wcj@csmu.edu.tw.
authors.forename: Chau-Jong
authors.initials: CJ
authors.lastname: Wang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008810:Mice, Inbred C57BL; D031653:Nelumbo / Q000737:chemistry*; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic / Q000187:drug effects; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry*; D010946:Plants, Medicinal; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; C526317:CCN2 protein, human; D010936:Plant Extracts; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D055513:Connective Tissue Growth Factor; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: Angiogenesis; Breast cancer; Connective tissue growth factor; Invasiveness; Nelumbo nucifera Gaertn