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© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

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.

Details

Title
Myricetin Suppresses the Propagation of Hepatocellular Carcinoma via Down-Regulating Expression of YAP
Author
Li, Minjing 1 ; Chen, Jinliang 2 ; Yu, Xiaofei 1 ; Sen, Xu 3 ; Li, Defang 1   VIAFID ORCID Logo  ; Zheng, Qiusheng 1   VIAFID ORCID Logo  ; Yin, Yancun 2 

 Institute of Integrated Medicine, Binzhou Medical University, Yantai 264003, China 
 School of Basic Medical Sciences, Binzhou Medical University, Yantai 264003, China 
 Key Laboratory of Tumour Molecular Biology, Department of Clinical Medicine, Binzhou Medical University, Yantai 264003, China 
First page
358
Publication year
2019
Publication date
2019
Publisher
MDPI AG
e-ISSN
20734409
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2548327794
Copyright
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.