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

作者全名："Zhang, Dingyue; Dong, Lixia; Yang, Wenyong; Wang, Kui"

作者地址："[Zhang, Dingyue; Dong, Lixia; Wang, Kui] Sichuan Univ, West China Sch Basic Med Sci & Forens Med, Chengdu 610041, Peoples R China; [Yang, Wenyong] Southwest Jiaotong Univ, Chengdu Hosp Affiliated 2, Peoples Hosp Chengdu 3, Med Res Ctr,Affiliated Hosp,Chongqing Med Univ,Dep, Chengdu 610041, Peoples R China"

通信作者："Wang, K (通讯作者)，Sichuan Univ, West China Sch Basic Med Sci & Forens Med, Chengdu 610041, Peoples R China.; Yang, WY (通讯作者)，Southwest Jiaotong Univ, Chengdu Hosp Affiliated 2, Peoples Hosp Chengdu 3, Med Res Ctr,Affiliated Hosp,Chongqing Med Univ,Dep, Chengdu 610041, Peoples R China."

来源：AUSTRALIAN JOURNAL OF CHEMISTRY

ESI学科分类：CHEMISTRY

WOS号：WOS:000994232300001

JCR分区：Q3

影响因子：1.1

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：agrimol B; anticancer agents; hepatocellular carcinoma; herbal drugs; molecular docking; network pharmacology; NQO1; target identification

摘要："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."

基金机构："Chinese NSFC [81872277, 82073081, 82273122]; Guangdong Basic and Applied Basic Research Foundation [2019B030302012]; 1.3.5 project of excellent development of discipline of West China Hospital of Sichuan University [ZYYC21001]"

基金资助正文："This research was funded by the Chinese NSFC (81872277, 82073081, 82273122), Guangdong Basic and Applied Basic Research Foundation (2019B030302012), and 1.3.5 project of excellent development of discipline of West China Hospital of Sichuan University (ZYYC21001)."