Myricetin Suppresses the Propagation of Hepatocellular Carcinoma via Down-Regulating Expression of YAP

Autor: Minjing Li, Jinliang Chen, Xiaofei Yu, Sen Xu, Defang Li, Qiusheng Zheng, Yancun Yin
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Cells, Vol 8, Iss 4, p 358 (2019)
Druh dokumentu: article
ISSN: 2073-4409
DOI: 10.3390/cells8040358
Popis: Myricetin is a naturally occurring flavonoid with protective effects against a variety of cancers. However, the molecular mechanism of myricetin against hepatocellular carcinoma (HCC) has still not been fully elucidated. Previous studies have indicated that YAP is essential for cancer initiation and progression. However, whether YAP contributes to the anti-cancer effects of myricetin remains unclear. Herein, we aimed to investigate the effect of myricetin on HCC, and identify the underlying mechanisms. We report that myricetin induced apoptosis and proliferation inhibition in HepG2 and Huh-7 cells. Myricetin inhibited expression of YAP by promoting its phosphorylation and subsequent degradation. Myricetin inhibited YAP expression by stimulating kinase activation of LATS1/2. Knockdown expression of LATS1/2 by shRNA attenuated myricetin-induced phosphorylation and degradation of YAP. Furthermore, myricetin sensitized HCC cells to cisplatin treatment through inhibiting YAP and its target genes, both in vitro and in vivo. The identification of the LATS1/2-YAP pathway as a target of myricetin may help with the design of novel strategies for human HCC prevention and therapy.
Databáze: Directory of Open Access Journals
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