Clinical and Translational Research
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Nov 6, 2022; 10(31): 11299-11312
Published online Nov 6, 2022. doi: 10.12998/wjcc.v10.i31.11299
Screening of traditional Chinese medicine monomers as ribonucleotide reductase M2 inhibitors for tumor treatment
Ya-Ya Qin, Song Feng, Xiao-Dong Zhang, Bin Peng
Ya-Ya Qin, Xiao-Dong Zhang, Department of Neurology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
Song Feng, Bin Peng, School of Basic Medicine, North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
Author contributions: Qin YY wrote the manuscript, designed the study, and acquired data; Feng S acquired, analyzed, and interpreted the data; Zhang XD supervised, reviewed, and edited the manuscript; Peng B designed and coordinated the study, collected funds; all authors approved the final draft.
Supported by Nanchong City School’s Science and Technology Strategic Cooperation, China, No. 20SXQT0304; Research and Development Project Plan of Affiliated Hospital of North Sichuan Medical College, China, No. 2020ZD003.
Institutional review board statement: Not applicable.
Informed consent statement: Not applicable.
Conflict-of-interest statement: All authors declare that they have no conflicts of interest.
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: Bin Peng, MD, Professor, School of Basic Medicine, North Sichuan Medical College, No. 234 Fujiang Road, Shunqing District, Nanchong 637000, Sichuan Province, China. binpeng01@sina.com
Received: June 23, 2022
Peer-review started: June 23, 2022
First decision: September 5, 2022
Revised: September 14, 2022
Accepted: September 29, 2022
Article in press: September 29, 2022
Published online: November 6, 2022
Processing time: 126 Days and 0.9 Hours
Abstract
BACKGROUND

Ribonucleotide reductase (RR) is a key enzyme in tumor proliferation, especially its subunit-RRM2. Although there are multiple therapeutics for tumors, they all have certain limitations. Given their advantages, traditional Chinese medicine (TCM) monomers have become an important source of anti-tumor drugs. Therefore, screening and analysis of TCM monomers with RRM2 inhibition can provide a reference for further anti-tumor drug development.

AIM

To screen and analyze potential anti-tumor TCM monomers with a good binding capacity to RRM2.

METHODS

The Gene Expression Profiling Interactive Analysis database was used to analyze the level of RRM2 gene expression in normal and tumor tissues as well as RRM2's effect on the overall survival rate of tumor patients. TCM monomers that potentially act on RRM2 were screened via literature mining. Using AutoDock software, the screened monomers were docked with the RRM2 protein.

RESULTS

The expression of RRM2 mRNA in multiple tumor tissues was significantly higher than that in normal tissues, and it was negatively correlated with the overall survival rate of patients with the majority of tumor types. Through literature mining, we discovered that berberine, ursolic acid, gambogic acid, cinobufagin, quercetin, daphnetin, and osalmide have inhibitory effects on RRM2. The results of molecular docking identified that the above TCM monomers have a strong binding capacity with RRM2 protein, which mainly interacted through hydrogen bonds and hydrophobic force. The main binding sites were Arg330, Tyr323, Ser263, and Met350.

CONCLUSION

RRM2 is an important tumor therapeutic target. The TCM monomers screened have a good binding capacity with the RRM2 protein.

Keywords: Tumor; Ribonucleotide reductase M2 inhibitor; Traditional Chinese medicine; Monomer; Molecular docking; Literature mining

Core Tip: Tumors seriously threaten human life and health. In our work, we found that ribonucleotide reductase M2 (RRM2) is highly expressed in most tumor tissues, and is related to poor prognosis. Seven traditional Chinese medicine monomers with good binding ability to RRM2 were identified, and their binding sites were summarized and analyzed. Those will provide ideas for the development of anti-tumor drugs with RRM2 inhibition in the future.