Network Pharmacology and Molecular Docking-Based Investigation: Prunus mume Against Colorectal Cancer via Silencing RelA Expression.

Minfeng Zhou,Fengxia Liang,Zhaomin Yu,Dan Luo,Rui Chen,Haiming Zhang,Qiumeng Li,Jinxiao Li,Youlin Chen

doi:10.3389/fphar.2021.761980

Abstract

Colorectal cancer (CRC) is one of the most pervasive cancers in the human disease spectrum worldwide, ranked the second most common cause of cancer death by the end of 2020. Prunus mume (PM) is an essential traditional Chinese medicine for the adjuvant treatment of solid tumors, including CRC. In the current study, we utilize means of network pharmacology, molecular docking, and multilayer experimental verification to research mechanism. The five bioactive compounds and a total of eight critical differentially expressed genes are screened out using the bioinformatics approaches of Cytoscape software, String database, Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes pathways, and molecular docking. RelA has been proven to be highly expressed in CRC. Experiments in vitro have shown that kaempferol, the main active component of PM, dramatically inhibited the growth, migration, and invasion of CRC cells, and experiments in vivo have shown that PM effectively delays CRC formation and improves the survival cycle of mice. Further analysis shows that PM inhibits the CRC progression by down-regulating the expression level of RelA, Bax, caspase 3, caspase 9, and EGFR in CRC. PM and its extract are potentially effective therapeutics for the treatment of CRC via the RelA/nuclear factor κB signaling pathway.

Highlights

Colorectal cancer (CRC) without obvious symptoms expresses early the main symptoms of occult or overt rectal bleeding, anemia, change in defecation habits, or abdominal pain in an advanced period (Dekker et al, 2019)
Data of Prunus mume (PM) and differential gene expression (DGE) in CRC were obtained from Traditional Chinese Medicine Database and Analysis Platform (TCMSP) and GEO databases
We found that PM possesses an adequate therapeutic effect on CRC, primarily by inhibiting RelA expression and NF-κB pathway from promoting tumor apoptosis

Summary

Introduction

Colorectal cancer (CRC) without obvious symptoms expresses early the main symptoms of occult or overt rectal bleeding, anemia, change in defecation habits, or abdominal pain in an advanced period (Dekker et al, 2019). CRC had been ranked the second most common cause of cancer death in America by 2020. As screening programs and colonoscopies increase, CRC morbidity and mortality are stabilized and decline in developed countries. With progress in developing countries, the global incidence of CRC will continue to increase (Bray et al, 2018; Dekker et al, 2019). The CRC incidence continues to rise in countries with medium to high human development index (HDI) (Wong et al, 2021). Unreasonable diet structure, overweight, physical inactivity, smoking, ultraviolet radiation, and cancer-related infections are modifiable factors leading to the development of CRC (Islami et al, 2018). Traditional Chinese herbal medicine (CHM) is expected to play a role in reducing toxicity and enhancing efficacy in the treatment of CRC

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