Suppression of Hepatocellular Carcinoma Progression through FOXM1 and EMT Inhibition via Hydroxygenkwanin-Induced miR-320a Expression.

Abstract

Daphne genkwa, a Chinese medicinal herb, is used frequently in Southeast Asian countries to treat diseases; the flavonoid hydroxygenkwanin (HGK) is extracted from its flower buds. The bioactivity of HGK, particularly as an anti-liver cancer agent, has not been explored. In this study, human hepatocellular carcinoma (HCC) cell lines and an animal xenograft model were employed to investigate both the activity of HGK against liver cancer and its cellular signaling mechanisms. HCC cells treated with HGK were subjected to cell function assays. Whole transcriptome sequencing was used to identify genes whose expression was influenced by HGK, and the flavonoid's cancer suppression mechanisms were further investigated through gain- and loss-of-function assays. Finally, in vitro findings were tested in a mouse xenograft model. The data showed that HGK induced the expression of the microRNA miR-320a, which in turn inhibited the expression of the transcription factor 'forkhead box protein M1' (FOXM1) and downstream FOXM1-regulated proteins related to epithelial-mesenchymal transition, thereby leading to the suppression of liver cancer cell growth and invasion. Significant inhibition of tumor growth was also observed in HGK-treated mice. Hence, the present study demonstrated the activity of HGK against liver cancer and validated its potential use as a therapeutic agent.

• Authors: Li-Fang Chou, Chi-Yuan Chen, Wan-Hua Yang, Chin-Chuan Chen, Junn-Liang Chang, Yann-Lii Leu, Miaw-Jene Liou, Tong-Hong Wang
• Journal: Biomolecules (Biomolecules) Vol. 10 Issue 1 (12 21 2019) ISSN: 2218-273X [Electronic] Switzerland
• PMID: 31877715 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Drugs, Chinese Herbal
• Flavonoids
• Forkhead Box Protein M1
• MIRN320 microRNA, human
• MicroRNAs
• hydroxygenkwanin

Topics

• Animals
• Carcinoma, Hepatocellular (drug therapy, genetics, metabolism, physiopathology)
• Daphne (chemistry)
• Drugs, Chinese Herbal (administration & dosage)
• Epithelial-Mesenchymal Transition (drug effects)
• Flavonoids (administration & dosage)
• Forkhead Box Protein M1 (genetics, metabolism)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Liver Neoplasms (drug therapy, genetics, metabolism, physiopathology)
• Male
• Mice, Nude
• MicroRNAs (genetics, metabolism)