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©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
Epigallocatechin gallate inhibits dimethylhydrazine-induced colorectal cancer in rats
Yu Wang, Hei-Ying Jin, Ming-Zhi Fang, Xiao-Feng Wang, Hao Chen, Shu-Liang Huang, De-Song Kong, Min Li, Xiu Zhang, Yu Sun, Shui-Ming Wang
Yu Wang, Ming-Zhi Fang, Min Li, Department of Oncology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210001, Jiangsu Province, China
Hei-Ying Jin, Department of Colorectal Surgery, The Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210000, Jiangsu Province, China
Xiao-Feng Wang, Hao Chen, Shui-Ming Wang, National Center of Colorectal Disease, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210001, Jiangsu Province, China
Shu-Liang Huang, Department of Pathology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210022, Jiangsu Province, China
De-Song Kong, Scientific Research Administration Department, Nanjing Hospital of Chinese Medicine affiliated to Nanjing University of Chinese Medicine, Nanjing 210001, Jiangsu Province, China
Xiu Zhang, Endoscopy Center, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210001, Jiangsu Province, China
Yu Sun, Origin Bioscience Inc, Nanjing 210000, Jiangsu Province, China
Author contributions: Wang Y and Wang SM conceived and designed the study; Jin HY, Fang MZ, Wang XF, and Chen H performed the experiments; Wang Y, Li M, and Kong DS wrote the article; Huang SL, Zhang X, and Sun Y coordinated the study and analyzed the data; all the authors contributed to, read, and approved the final manuscript.
Supported by Nursing Advantage Discipline Construction Project Foundation of Jiangsu Province University, No. 2019YSHL107; Nanjing Medical Science and Technique Development Foundation, No. NWQR-201705.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Southeast University (IACUC protocol number: 20161201006.
Conflict-of-interest statement: All the authors have no conflict of interest related to the manuscript.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Shui-Ming Wang, MD, PhD, Attending Doctor, Research Scientist, National Center of Colorectal Disease, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, No. 157, Daming Road, Qinhuai District, Nanjing 210001, Jiangsu Province, China. watershuiming@hotmail.com
Received: November 20, 2019
Peer-review started: November 20, 2019
First decision: January 7, 2020
Revised: February 13, 2020
Accepted: March 11, 2020
Article in press: March 11, 2020
Published online: May 7, 2020
BACKGROUND
Epigallocatechin gallate (EGCG) is a polyhydroxy phenolic compound extracted from tea and its antitumor effect has received widespread attention. We explored the inhibitory effect of EGCG on dimethylhydrazine (DMH)-induced colorectal cancer (CRC) using a rat model, predicted the interaction between EGCG and CRC target genes using a database, and explained the EGCG associated target pathways and mechanisms in CRC.
AIM
To understand the inhibitory mechanisms of EGCG on CRC cell proliferation and identify its pharmacological targets by network pharmacology analysis.
METHODS
DMH (40 mg/kg, s.c., twice weekly for eight weeks) was used to induce CRC in rats. After model establishment, the rats were administered with EGCG (50, 100, or 200 mg/kg, p.o., once daily for eight weeks) and killed 12 and 20 wk after the start of the experiment. Formation of aberrant crypt foci and tumor was studied by histological analysis. Using network pharmacology analysis, candidate and collective targets of EGCG and CRC were identified, and Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses were used to predict the pathways altered by EGCG.
RESULTS
At week 12, high-dose EGCG treatment significantly reduced the tumor formation rate, total number of tumors, cancerous and non-cancerous tumors, tumor volume, ascites formation, and aberrant crypt foci count. At week 20, all three doses of EGCG were effective. Seventy-eight collective targets of EGCG and CRC were identified, of which 28 genes were dysregulated in CRC. Kyoto Encyclopedia of Genes and Genomes and GO analyses showed that the dysregulated genes were enriched in hsa05210 (CRC), hsa04115 (p53 signaling pathway), and hsa04151 (PI3K-Akt signaling pathway), GO:0043124 (negative regulation of I-kappaB kinase/NF-kappaB signaling pathway), GO:0043409 (negative regulation of mitogen-activated protein kinase cascade), and GO:2001244 (positive regulation of intrinsic apoptotic signaling pathway) respectively.
CONCLUSION
EGCG inhibits the formation of DMH-induced CRC by regulating key pathways involved in tumorigenesis.
Core tip: Our research found that epigallocatechin gallate (EGCG) extracted from tea can inhibit the occurrence of colorectal cancer (CRC) in dimethylhydrazine-induced rat models and predicted the interaction between EGCG and CRC target genes using a bioinformatics database. The Cancer Genome Atlas database was used to further explore the significant differences of 28 genes among 78 intersection target genes and Kyoto Encyclopedia of Genes and Genomes and Gene ontology analyses were performed to explore the pathway and mechanism of EGCG on CRC.
