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©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
Curcumin for gastric cancer: Mechanism prediction via network pharmacology, docking, and in vitro experiments
Peng-Hui Yang, Ya-Nan Wei, Bi-Juan Xiao, Si-Yi Li, Xin-Long Li, Liang-Jun Yang, Hua-Feng Pan, Geng-Xin Chen
Peng-Hui Yang, Ya-Nan Wei, The Second School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong Province, China
Bi-Juan Xiao, Xin-Long Li, Hua-Feng Pan, Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong Province, China
Si-Yi Li, Department of Traditional Chinese Medicine, The People's Hospital of Longhua, Shenzhen 518109, Guangdong Province, China
Liang-Jun Yang, Department of Gastroenterology, Tongde Hospital of Zhejiang Province, Hangzhou 310012, Zhejiang Province, China
Geng-Xin Chen, Centre for Translational Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong Province, China
Author contributions: All authors contributed to the conceptualization and composition of this manuscript; Yang PH, Wei YN and Xiao BJ wrote the paper; Li SY, Li XL and Yang LJ assisted in data collection and analysis; Chen GX and Pan HF contributed to the study design; Chen GX made critical revisions to this paper; All authors have reviewed and approved the final version of the manuscript.
Supported by the National Nature Science Foundation of China, No. 81273735 and No. 82174319; the Natural Science Foundation of Guangdong Province, China, No. 2021A1515010961; the Key-Area Research and Development Program of Guangdong Province, China, No. 2020B1111100011; and the China Postdoctoral Science Foundation, China, No. 2023M740859.
Institutional animal care and use committee statement: The study did not involve any human or animal experiments, and the data is derived from cells or tissues experiments and databases. BGC-823 cell line used in the study was purchased from Guangzhou Jennio Biotech Co., Ltd, China.
Conflict-of-interest statement: The authors declare that there are no conflicts of interest regarding the publication of this paper. The authors affirm that this research is conducted in an unbiased manner and that the findings and conclusions presented are solely based on scientific merit.
Data sharing statement: No additional data are available.
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: Geng-Xin Chen, MD, Chief Doctor, Centre for Translational Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 111 Dade Road, Guangzhou 510120, Guangdong Province, China.
gxchen@gzucm.edu.cn
Received: April 15, 2024
Revised: May 24, 2024
Accepted: June 18, 2024
Published online: August 15, 2024
Processing time: 115 Days and 1.3 Hours
BACKGROUND
Curcumin originates from the natural herb turmeric, and its antitumor effects have been known about for a long time. However, the mechanism by which curcumin affects gastric cancer (GC) has not been elucidated.
AIM
To elucidate the potential mechanisms of curcumin in the treatment of GC.
METHODS
Network pharmacological approaches were used to perform network analysis of Curcumin. We first analyzed Lipinski’s Rule of Five for the use of Curcumin. Curcumin latent targets were predicted using the PharmMapper, SwissTargetPrediction and DrugBank network databases. GC disease targets were mined through the GeneCard, OMIM, DrugBank and TTD network databases. Then, GO enrichment, KEGG enrichment, protein-protein interaction (PPI), and overall survival analyses were performed. The results were further verified through molecular docking, differential expression analysis and cell experiments.
RESULTS
We identified a total of 48 curcumin-related genes with 31 overlapping GC-related targets. The intersection targets between curcumin and GC have been enriched in 81 GO biological processes and 22 significant pathways. Following PPI analysis, 6 hub targets were identified, namely, estrogen receptor 1 (ESR1), epidermal growth factor receptor (EGFR), cytochrome P450 family 3 subfamily A member 4 (CYP3A4), mitogen-activated protein kinase 14 (MAPK14), cytochrome P450 family 1 subfamily A member 2 (CYP1A2), and cytochrome p450 family 2 subfamily B member 6(CYP2B6). These factors are correlated with decreased survival rates among patients diagnosed with GC. Molecular docking analysis further substantiated the strong binding interactions between Curcumin and the hub target genes. The experimental findings demonstrated that curcumin not only effectively inhibits the growth of BGC-823 cells but also suppresses their proliferation. mRNA levels of hub targets CYP3A4, MAPK14, CYP1A2, and CYP2B6 in BGC-823 cells were significantly increased in each dose group.
CONCLUSION
Curcumin can play an anti-GC role through a variety of targets, pathways and biological processes.
Core Tip: This study aimed to elucidate the therapeutic mechanisms of curcumin in gastric cancer (GC). Through network pharmacology, core targets correlating to poor survival in patients with GC were identified, including estrogen receptor 1(ESR1),epidermal growth factor receptor (EGFR), cytochrome P450 family 3 subfamily A member 4 (CYP3A4), mitogen-activated protein kinase 14 (MAPK14), cytochrome P450 family 1 subfamily A member 2 (CYP1A2), and cytochrome p450 family 2 subfamily B member 6 (CYP2B6). Molecular docking confirmed the favorable interactions of curcumin with pivotal target genes. In vitro experiments validated the regulatory effects of curcumin on GC cells through these targets. The therapeutic efficacy of curcumin involves multitarget, multipathway, and multibiological processes, offering new insights into its clinical application in GC treatment.
