Issue 6, 2019

A curcumin derivative, WZ35, suppresses hepatocellular cancer cell growth via downregulating YAP-mediated autophagy

Abstract

Hepatocellular carcinoma (HCC) is a common cancer type throughout the world. Due to the high occurrence rate and mortality, liver cancer is one of the leading causes of cancer associated death. With the development of monoclonal antibodies and immunotherapy, the mortality of HCC cancer patients has reduced. However, the recurrence and outcomes of patients remain poor. Therefore, there is an urgent need to develop more effective drugs for HCC therapy. WZ35, a novel curcumin derivative, exhibits potential anti-tumor activity in gastric cancer cells by regulating ROS dependent JNK activation and ER stress. Here, we evaluated the tumor suppressive activity of WZ35 in hepatocellular carcinoma in vitro and in vivo. CCK-8 was used to detect cell viability with or without curcumin or WZ35; cell apoptosis was determined by flow cytometry analysis; GFP-LC3 plasmids were used to investigate the level of autophagy-associated LC3; siRNA transfection was applied to silence endogenous YAP; and western blot was performed to detect the alteration of indicated molecules. Bioinformatics analysis and IHC assay were applied to evaluate the YAP level in normal and liver cancer tissues. In this study, we found that WZ35 effectively suppresses HCC cancer cell growth in vitro and in vivo by promoting cell apoptosis. Importantly, downregulation of YAP contributes to WZ35 caused autophagy inhibition which is different from that of curcumin. We also confirmed that WZ35 is more effective at suppressing HCC cell growth in vivo. Finally, we confirmed that YAP was significantly overexpressed in liver cancer tissues. Collectively, these data indicate that WZ35 could be considered as a promising compound for HCC therapy.

Graphical abstract: A curcumin derivative, WZ35, suppresses hepatocellular cancer cell growth via downregulating YAP-mediated autophagy

Article information

Article type
Paper
Submitted
11 Dec 2018
Accepted
18 May 2019
First published
21 May 2019

Food Funct., 2019,10, 3748-3757

A curcumin derivative, WZ35, suppresses hepatocellular cancer cell growth via downregulating YAP-mediated autophagy

L. Wang, Z. Zhu, L. Han, L. Zhao, J. Weng, H. Yang, S. Wu, K. Chen, L. Wu and T. Chen, Food Funct., 2019, 10, 3748 DOI: 10.1039/C8FO02448K

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements