Ougan (Citrus reticulata cv. Suavissima) flavedo extract suppresses cancer motility by interfering with epithelial-to-mesenchymal transition in SKOV3 cells.

Linlin Chang, Sheng Jia, Yingying Fu, Tianyi Zhou, Ji Cao, Qiaojun He, Bo Yang, Xian Li, Chongde Sun, Dan Su, Hong Zhu, Kunsong Chen

文献索引：Chin. Med. 10 , 14, (2015)

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摘要

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).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.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).The anti-metastatic ability of OFE inhibited EMT by interfering with the canonical TGF-β1-SMAD-Snail/Slug axis.