title: Euphorbia humifusa Willd exerts inhibition of breast cancer cell invasion and metastasis through inhibition of TNFα-induced MMP-9 expression.
abstract: BACKGROUND
  Breast cancer is the most common type of malignancy in women worldwide. Euphorbia humifusa Willd (EuH) is a plant that is widely used as a traditional medicine. However, no systemic studies on the anti-cancer effects of EuH have been reported. The aim of this study is to evaluate the anti-metastatic effect of the EuH.
  
  
  METHODS
  Ethyl acetate fraction was prepared from EuH methanol extracts (EA/EuH). Inhibitory effect of EA/EuH on cell migration was determined using an in vitro scratch-wound healing assay. The anti-invasive activity was determined by in vitro three-dimensional spheroid culture system and in vivo syngenic experimental lung metastasis experiment. Gene expression profiles were analyzed by using RT-PCR, real-time PCR, and luciferase reporter assay systems.
  
  
  RESULTS
  Ethyl acetate fraction from the EuH extract (EA/EuH) inhibited the migration and invasive capabilities of highly metastatic MDA-MB-231 breast cancer cells and attenuated syngeneic lung metastasis of mouse 4 T1 breast cancer cells in vivo. Mechanistically, EA/EuH decreased tumor necrosis factor alpha (TNFα)-induced matrix metalloproteinase (MMP)-9 mRNA expression through the inhibition of NF-κB activity in MDA-MB-231 cells.
  
  
  CONCLUSIONS
  EuH may be beneficial in the prevention of invasion and metastasis of early stage breast cancer and can be served as an anti-metastatic agent or adjuvant therapy against metastatic breast cancer.
authors: Department of Biological Sciences, College of Biological Science and Biotechnology, Konkuk University, Seoul, Republic of Korea.|Cancer and Metabolism Institute, Konkuk University, Seoul, Republic of Korea.
authors: Soon Young
authors: SY
authors: Shin
authors: Cancer and Metabolism Institute, Konkuk University, Seoul, Republic of Korea.
authors: Chang Gun
authors: CG
authors: Kim
authors: Cancer and Metabolism Institute, Konkuk University, Seoul, Republic of Korea.
authors: You Jung
authors: YJ
authors: Jung
authors: Division of Bioscience and Biotechnology, College of Biological Science and Biotechnology, BMIC, Konkuk University, Seoul, Republic of Korea.
authors: Yearam
authors: Y
authors: Jung
authors: Division of Bioscience and Biotechnology, College of Biological Science and Biotechnology, BMIC, Konkuk University, Seoul, Republic of Korea.
authors: Hyeryoung
authors: H
authors: Jung
authors: Division of Bioscience and Biotechnology, College of Biological Science and Biotechnology, BMIC, Konkuk University, Seoul, Republic of Korea.
authors: Jihyun
authors: J
authors: Im
authors: Division of Bioscience and Biotechnology, College of Biological Science and Biotechnology, BMIC, Konkuk University, Seoul, Republic of Korea. yoongho@konkuk.ac.kr.|College of Biological Science and Biotechnology, Konkuk University, 120 Neundong-ro, Gwangjin-gu, Seoul, 05029, Republic of Korea. yoongho@konkuk.ac.kr.
authors: Yoongho
authors: Y
authors: Lim
authors: Department of Biological Sciences, College of Biological Science and Biotechnology, Konkuk University, Seoul, Republic of Korea. yhlee58@konkuk.ac.kr.|Cancer and Metabolism Institute, Konkuk University, Seoul, Republic of Korea. yhlee58@konkuk.ac.kr.|College of Biological Science and Biotechnology, Konkuk University, 120 Neundong-ro, Gwangjin-gu, Seoul, 05029, Republic of Korea. yhlee58@konkuk.ac.kr.
authors: Young Han
authors: http://orcid.org/0000-0003-4060-6587
authors: YH
authors: Lee
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D028481:Euphorbia / Q000737:chemistry*; D005260:Female; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D009361:Neoplasm Invasiveness; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D020780:Matrix Metalloproteinase 9
keywords: Euphorbia humifusa Willd; Invasion; Matrix metalloproteinase-9; Metastasis; Nuclear factor-kappa B; Tumor necrosis factor alpha