Feasibility of the Inhibitor Development for Cancer: A Systematic Approach for Drug Design
Yu Jiang, Ling Liu, Yichao Geng, Qingsong Li, Daxian Luo, Li Liang, Wei Liu, Weiwei Ouyang, Jianping Hu
Abstract
The traditional Chinese medicine (TCM) bupleurum-ginger-licorice formula presents significant anti-cancer effects, but its active ingredients and inhibitory mechanism remain unclear. In this work, the core effective ingredient quercetin and its signal transducer and activator of transcription 3 (Stat3) receptor both were identified by network pharmacology. Quercetin is a low-toxicity, non-carcinogenic flavonoid with antioxidant, anti-inflammatory and anticancer activities, which is widely distributed in edible plants.
Introduction
The nature of cancer is the continuous and uncontrolled proliferation of cells, usually caused by increased conversion of proto-oncogenes to oncogenes or by attenuated mutations in tumor suppressor genes. According to the World Health Organization’s (WHO) annual report for 2023, there were 25.6 million new cancer cases and 12 million cancer deaths globally, making it the second leading cause of death after cardiovascular disease. The incidence of six of the top 10 cancers continues to increase, of these, breast cancer is by far the most commonly diagnosed malignant tumor, with an estimated 2.3 million new cases (11.7%), followed by lung cancer (11.4%), colorectal cancer (10.0%), prostate cancer (7.3%), stomach cancer (5.6%), and liver cancer (4.1%).
Materials and Methods:
Network pharmacology has been widely applied into the field of TCM, which can effectively predict the core components, action targets, toxicity and side effects of drugs. Specifically, after searching the relevant databases, six main steps were performed: To determine the chemical composition of the TCM, this study first collected the chemical structures and potential targets of the active ingredients in the TCM bupleurum-ginger-licorice formula from the TCMSP database (http://lsp.nwu.edu.cn/tcmsp.php); In this integrated pharmacophore matching database with frequent updates, target compounds were screened by respectively setting oral bioavailability (OB) and drug likeness (DL) scores greater than 30% and 0.18, and the same molecules were removed by structural overlap.
Discussion
There are definitely two questions in cancer biology. First, the causes of cancer are based on genetic mutations and multiple carcinogenic progressions; the second is how to treat cancer? Therefore, in this paper cancer is targeted through herbal agents. In conclusion, the herbal formula of bupleurum, ginger and licorice has good ability to treat cancer, which has multi-component, multi-target and multi-pathway characteristics. Based on the network pharmacological analysis, the active ingredients quercetin, licorice chalcone and a series of possible anticancer targets of the three herbal medicines (bupleurum, ginger and licorice) were identified.
Citation: Jiang Y, Liu L, Geng Y, Li Q, Luo D, Liang L, et al. (2024) Feasibility of the inhibitor development for cancer: A systematic approach for drug design. PLoS ONE 19(8): e0306632. https://doi.org/10.1371/journal.pone.0306632
Editor: Jorddy Neves Cruz, Universidade Federal do Para, BRAZIL
Received: December 28, 2023; Accepted: June 20, 2024; Published: August 22, 2024.
Copyright: © 2024 Jiang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: If the data are all contained within the manuscript and/or Supporting Information files, enter the following: All relevant data are within the manuscript and its Supporting Information files.
Funding: This work was supported by the following fundings: National Natural Science Foundation of China (31870655) and Sichuan Science and Technology Program (2019YFH0054) provided financial support. The funders had role in study design. Thank you very much for your processing. We appreciate your time and look forward to your response.
Competing interests: The authors have declared that no competing interests exist.
