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Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Chin+Med 2015 ; 10 (ä): ä Nephropedia Template TP
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Ougan (Citrus reticulata cv Suavissima) flavedo extract suppresses cancer motility by interfering with epithelial-to-mesenchymal transition in SKOV3 cells #MMPMID26131016
Chang L; Jia S; Fu Y; Zhou T; Cao J; He Q; Yang B; Li X; Sun C; Su D; Zhu H; Chen K
Chin Med 2015[]; 10 (ä): ä PMID26131016show ga
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 ?g/mL and 20 ?g/mL, using qRT-PCR and western blot analyses. Results: Non-cytotoxic concentrations of OFE significantly suppressed the cellular migration (4 ?g/mL, P?=?0.005 vs. control group; 20 ?g/mL, P?=?0.003 vs. control group) and motility (4 ?g/mL, P?0.001 vs. control group; 20 ?g/mL, P?0.001 vs. control group) of SKOV3 cells, and inhibited transforming growth factor-?1 (TGF-?1)-induced E-cadherin loss (4 ?g/mL, P?=?0.002 vs. control group; 20 ?g/mL, P?=?0.001 vs. control group) and mesenchymal marker upregulation, e.g., N-cadherin (4 ?g/mL, P?=?0.027 vs. control group; 20 ?g/mL, P?=?0.013 vs. control group), vimentin (4 ?g/mL, P?=?0.036 vs. control group; 20 ?g/mL, P?=?0.015 vs. control group) and fibronectin (4 ?g/mL, P?0.001 vs. control group; 20 ?g/mL, P?0.001 vs. control group). Conclusions: The anti-metastatic ability of OFE inhibited EMT by interfering with the canonical TGF-?1-SMAD-Snail/Slug axis.