Diospyros kaki leaves inhibit HGF/Met signaling-mediated EMT and stemness features in hepatocellular carcinoma. (August 2020)

• Record Type: Journal Article
• Authors: Ko, Hyeonseok; Huh, Gyuwon; Jung, Sang Hoon; Kwon, Hyukjoon; Jeon, Youngsic; Park, Young Nyun; Kim, Young-Joo
• Is Part Of: Food and chemical toxicology. Volume 142(2020)
• Publication Date: 2020-08
• Subjects: Diospyros kaki leaves -- Hepatocellular carcinoma -- EMT -- Stemness -- HGF/Met signaling; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2020.111475
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: Persimmon ( Diospyros kaki L.f.) trees are widely cultivated for their edible fruits in Asia. D. kaki leaves are abundant in phytochemicals that have numerous medicinal properties. Hepatocyte growth factor (HGF) and its receptor Met lead to poor prognosis via the promotion of metastasis and chemoresistance in hepatocellular carcinoma (HCC). Therefore, inhibitors targeting the HGF/Met pathway are regarded as promising drugs against HCC. Here, we investigated the effects of D. kaki leaves on HGF-induced epithelial-to-mesenchymal transition (EMT) and stemness traits in HCC. The ethanol extract of D. kaki leaves (EEDK) markedly suppressed HGF-mediated cell migration and invasion through upregulation of CDH1 and downregulation of SNAI1, VIM, MMP1, MMP2, and MMP9 . Moreover, EEDK increased the cytotoxicity of sorafenib, which was reduced by HGF, and decreased the expression of the stemness markers KRT19 and CD44 . Additionally, we found a clear correlation between stemness and EMT markers in HCC patients. Importantly, EEDK reduced Met activity and attenuated HGF-mediated activation of JNK/c-Jun. Our findings provide new evidence that EEDK can ameliorate HCC with poor prognosis and aggressive phenotype by blocking HGF/Met signaling. Graphical abstract: Image 1 Highlights: This research used Diospyros kaki leaves containing a various phytochemicals that have known medicinal properties. Ethanol extract of Diospyros kaki leaves (EEDK) had an inhibitory effect on HGF-induced EMT and stemness features in HCC. EEDK attenuated HGF/Met signaling, especially JNK/c-Jun activation.