title: Ougan (Citrus reticulata cv. Suavissima) flavedo extract suppresses cancer motility by interfering with epithelial-to-mesenchymal transition in SKOV3 cells.
abstract: BACKGROUND
  Ougan (Citrus reticulata cv. Suavissima) flavedo extract (OFE) exhibited potential anti-tumor effects with unclear underlying mechanisms. This study aims to evaluate the potential anti-metastatic activities of OFE on human ovarian cancer cells, and investigate its inhibitory effect on epithelial-to-mesenchymal transition (EMT).
  
  
  METHODS
  Ougan fruits were harvested. Flavedo tissues were separated and made into freeze-dried powder. Then OFE were extracted from the powder. The components of OFE were identified by the high performance liquid chromatography system with a detection wavelength of 280 nm for flavanones and 330 nm for polymethoxylated flavones. Cell viability was assessed by Sulforhodamine B assay. The effects on cancer cell migration and motility were evaluated by wound-healing and transwell assays. The mechanisms of action were investigated by examining the modulation by OFE on EMT-related signaling pathways at the concentrations of 4 μg/mL and 20 μg/mL, using qRT-PCR and western blot analyses.
  
  
  RESULTS
  Non-cytotoxic concentrations of OFE significantly suppressed the cellular migration (4 μg/mL, P = 0.005 vs. control group; 20 μg/mL, P = 0.003 vs. control group) and motility (4 μg/mL, P < 0.001 vs. control group; 20 μg/mL, P < 0.001 vs. control group) of SKOV3 cells, and inhibited transforming growth factor-β1 (TGF-β1)-induced E-cadherin loss (4 μg/mL, P = 0.002 vs. control group; 20 μg/mL, P = 0.001 vs. control group) and mesenchymal marker upregulation, e.g., N-cadherin (4 μg/mL, P = 0.027 vs. control group; 20 μg/mL, P = 0.013 vs. control group), vimentin (4 μg/mL, P = 0.036 vs. control group; 20 μg/mL, P = 0.015 vs. control group) and fibronectin (4 μg/mL, P < 0.001 vs. control group; 20 μg/mL, P < 0.001 vs. control group).
  
  
  CONCLUSIONS
  The anti-metastatic ability of OFE inhibited EMT by interfering with the canonical TGF-β1-SMAD-Snail/Slug axis.
authors.affiliation: Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Chang
authors.affiliation: Laboratory of Fruit Quality Biology/The State Agriculture Ministry Laboratory of Horticultural Plant Growth, Development and Quality Improvement, Zhejiang University, Hangzhou, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Jia
authors.affiliation: Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Tianyi
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Cao
authors.affiliation: Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Qiaojun
authors.initials: Q
authors.lastname: He
authors.affiliation: Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: Laboratory of Fruit Quality Biology/The State Agriculture Ministry Laboratory of Horticultural Plant Growth, Development and Quality Improvement, Zhejiang University, Hangzhou, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Li
authors.affiliation: Laboratory of Fruit Quality Biology/The State Agriculture Ministry Laboratory of Horticultural Plant Growth, Development and Quality Improvement, Zhejiang University, Hangzhou, China.
authors.forename: Chongde
authors.initials: C
authors.lastname: Sun
authors.affiliation: Zhejiang Cancer Hospital, Hangzhou, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Su
authors.affiliation: Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Laboratory of Fruit Quality Biology/The State Agriculture Ministry Laboratory of Horticultural Plant Growth, Development and Quality Improvement, Zhejiang University, Hangzhou, China.
authors.forename: Kunsong
authors.initials: K
authors.lastname: Chen