Ko, Hyeonseok Huh, Gyuwon Jung, Sang Hoon Kwon, Hyukjoon Jeon, Youngsic Park, Young Nyun Kim, Young-Joo 2024-01-19T17:01:46Z 2024-01-19T17:01:46Z 2021-09-05 2020-08 0278-6915 https://pubs.kist.re.kr/handle/201004/118296 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 HGFmediated 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. English PERGAMON-ELSEVIER SCIENCE LTD EPITHELIAL-MESENCHYMAL TRANSITION CADHERIN EXPRESSION PERSIMMON INVASION METASTASIS EXTRACT CELLS MET L. ACTIVATION Diospyros kaki leaves inhibit HGF/Met signaling-mediated EMT and stemness features in hepatocellular carcinoma Article 10.1016/j.fct.2020.111475 1 FOOD AND CHEMICAL TOXICOLOGY, v.142 FOOD AND CHEMICAL TOXICOLOGY 142 scie scopus 000550060200017 2-s2.0-85086474583 Food Science & Technology Toxicology Food Science & Technology Toxicology Article EPITHELIAL-MESENCHYMAL TRANSITION CADHERIN EXPRESSION PERSIMMON INVASION METASTASIS EXTRACT CELLS MET L. ACTIVATION Diospyros kaki leaves Hepatocellular carcinoma EMT Sternness HGF/Met signaling