Clinical and Translational Research
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Aug 15, 2024; 16(8): 3539-3558
Published online Aug 15, 2024. doi: 10.4251/wjgo.v16.i8.3539
Targeting colorectal cancer with Herba Patriniae and Coix seed: Network pharmacology, molecular docking, and in vitro validation
Cheng-Lei Wang, Bing-Wei Yang, Xin-Yan Wang, Xue Chen, Wei-Dong Li, Hao-Yu Zhai, Ying Wu, Mu-Yao Cui, Jia-He Wu, Qing-Hui Meng, Nan Zhang
Cheng-Lei Wang, Bing-Wei Yang, Xin-Yan Wang, Xue Chen, Wei-Dong Li, Hao-Yu Zhai, Mu-Yao Cui, Jia-He Wu, Department of Oncology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
Cheng-Lei Wang, Ying Wu, The First Clinical Medical College, Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi Province, China
Wei-Dong Li, Department of Scientific Research Management, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
Qing-Hui Meng, School of Clinical Medicine Qinghai University, Xining 810000, Qinghai Province, China
Nan Zhang, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China
Co-first authors: Cheng-Lei Wang and Bing-Wei Yang.
Author contributions: Li WD was the main contributor to study design and management; Wang CL, Yang BW, and Wang XY conducted the experiments and drafted the manuscript; Chen X, Zhai HY, and Wu Y participated in data collection and figure preparation; Cui MY, Wu JH, Meng QH, and Zhang N participated in discussions and revised the manuscript; and all authors read and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 82174464; China Academy of Traditional Chinese Medicine Science and Technology Innovation Project, No. CI2021A01806; and Central High Level Traditional Chinese Medicine Hospital Clinical Research and Achievement Transformation Ability Enhancement Project, No. HLCMHPP2023085.
Conflict-of-interest statement: Authors have no conflicts of interest to declare.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Wei-Dong Li, MD, Chief Doctor, Department of Scientific Research Management, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, No. 5 Beixiange, Xicheng District, Beijing 100053, China. liweidongdoctor@hotmail.com
Received: April 23, 2024
Revised: May 27, 2024
Accepted: June 17, 2024
Published online: August 15, 2024
Processing time: 106 Days and 17 Hours
Abstract
BACKGROUND

Herba Patriniae and Coix seed (HC) constitute a widely utilized drug combination in the clinical management of colorectal cancer (CRC) that is known for its diuretic, anti-inflammatory, and swelling-reducing properties. Although its efficacy has been demonstrated in a clinical setting, the active compounds and their mechanisms of action in CRC treatment remain to be fully elucidated.

AIM

To identify the active, CRC-targeting components of HC and to elucidate the mechanisms of action involved.

METHODS

Active HC components were identified and screened using databases. Targets for each component were predicted. CRC-related targets were obtained from human gene databases. Interaction targets between HC and CRC were identified. A “drug-ingredient-target” network was created to identify the core components and targets involved. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to elucidate the key pathways involved. Molecular docking between core targets and key components was executed. In vitro experiments validated core monomers.

RESULTS

Nineteen active components of HC were identified, with acacetin as the primary active compound. The predictive analysis identified 454 targets of the active compounds in HC. Intersection mapping with 2685 CRC-related targets yielded 171 intervention targets, including 30 core targets. GO and KEGG analyses indicated that HC may influence the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. Molecular docking showed that acacetin exhibited an optimal interaction with AKT1, identifying PI3K, AKT, and P53 as key genes likely targeted by HC during CRC treatment. Acacetin inhibited HT-29 cell proliferation and migration, as well as promoted apoptosis, in vitro. Western blotting analysis revealed increased p53 and cleaved caspase-3 expression and decreased levels of p-PI3K, p-Akt, and survivin, which likely contributed to CRC apoptosis.

CONCLUSION

Acacetin, the principal active compound in the HC pair, inhibited the proliferation and migration of HT-29 cells and promoted apoptosis through the PI3K/Akt/p53 signaling pathway.

Keywords: Colorectal cancer; Baijiangcao (Herba Patriniae); Yiyiren (Coix seed); Acacetin; Proliferation; Migration; Apoptosis; Network pharmacology

Core Tip: We identified acacetin as the key active ingredient of “Herba Patriniae and Coix seed.” Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses suggested that “Herba Patriniae and Coix seed” acts on colorectal cancer (CRC) through the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway, and molecular docking showed that the best docking effect was between acacetin and AKT1. In vitro experiment results corroborated that acacetin inhibits the proliferation and migration, and promotes apoptosis of CRC cells through the PI3K/Akt/p53 signaling pathway.