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RESEARCH ARTICLE
Contents Vol 76(8)

Identification of NQO1 as a target of herbal drug agrimol B in hepatocellular carcinoma

Dingyue Zhang A # , Lixia Dong A # , Wenyong Yang B * and Kui Wang https://orcid.org/0000-0003-3503-1563 A *
+ Author Affiliations
- Author Affiliations

A West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, 610041, P. R. China.

B Department of Neurosurgery, Medical Research Center, The Third People’s Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, The Second Chengdu Hospital Affiliated to Chongqing Medical University, Chengdu, 610041, P. R. China.

* Correspondence to: kuiwang@scu.edu.cn, ywenyong@hotmail.com
# These authors contributed equally to this paper

Handling Editor: Mibel Aguilar

Australian Journal of Chemistry 76(8) 465-475 https://doi.org/10.1071/CH22255
Submitted: 2 December 2022  Accepted: 19 April 2023   Published: 24 May 2023

© 2023 The Author(s) (or their employer(s)). Published by CSIRO Publishing.

Abstract

Agrimol B is a small molecule isolated from traditional Chinese herbal medicine with a potential anti-cancer effect. However, the molecular target of agrimol B remains unclear. In this report, we found that agrimol B inhibits the growth of hepatocellular carcinoma (HCC) cells. A combination of network pharmacology strategy, bioinformatics analysis, molecular docking and target validation experiments was performed to identify and verify the protein targets of agrimol B in HCC. Bioinformatics analysis suggests that the activity of agrimol B against HCC was related to a cellular response to chemical stress and oxidative stress, folate biosynthesis, the complement and coagulation cascade and FoxO signaling pathway. We further identified 10 core targets through network pharmacology analysis. Among them, NAD(P)H: quinone dehydrogenase 1 (NQO1) was screened as the most promising target based on a molecular docking analysis. The interaction between agrimol B and NQO1 was corroborated by a cellular thermal shift assay. In addition, agrimol B inhibited the growth of HCC cells by decreasing NQO1 activity. Taken together, we identified NQO1 as a molecular target of agrimol B, which provides a new insight into the anti-cancer mechanism of agrimol B in HCC.

Keywords: agrimol B, anticancer agents, hepatocellular carcinoma, herbal drugs, molecular docking, network pharmacology, NQO1, target identification.


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