Unveiling the Mechanism of the ChaiShao Shugan Formula Against Triple-Negative Breast Cancer

Teng Fan; Yuanyuan Huang; Zeyu Liu; Jinsheng Huang; Bin Ke; Yuming Rong; Huijuan Qiu; Bei Zhang

doi:10.2147/DDDT.S394287

Unveiling the Mechanism of the ChaiShao Shugan Formula Against Triple-Negative Breast Cancer

Drug Des Devel Ther. 2024 Apr 10:18:1115-1131. doi: 10.2147/DDDT.S394287. eCollection 2024.

Authors

Teng Fan^#^{1

2

3}, Yuanyuan Huang^#^{1

2

3}, Zeyu Liu^#^{1

2}, Jinsheng Huang^{1

2}, Bin Ke^{1

2

3}, Yuming Rong^{1

2}, Huijuan Qiu^{1

2}, Bei Zhang^{1

2

3}

Affiliations

¹ TCM&VIP Department, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.
² State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.
³ Integrated Traditional Chinese and Western Medicine Research Center, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.

^# Contributed equally.

Abstract

Background: The ChaiShao Shugan Formula (CSSGF) is a traditional Chinese medicine formula with recently identified therapeutic value in triple-negative breast cancer (TNBC). This study aimed to elucidate the underlying mechanism of CSSGF in TNBC treatment.

Methods: TNBC targets were analyzed using R and data were from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The major ingredients and related protein targets of CSSGF were explored via the Traditional Chinese Medicine Systems Pharmacology database, and an ingredient-target network was constructed via Cytoscape to identify hub genes. The STRING database was used to construct the PPI network. GO and KEGG enrichment analyses were performed via R to obtain the main targets. The online tool Kaplan‒Meier plotter was used to identify the prognostic genes. Molecular docking was applied to the core target genes and active ingredients. MDA-MB-231 and MCF-7 cell lines were used to verify the efficacy of the various drugs.

Results: A total of 4562 genes were screened as TNBC target genes. The PPI network consisted of 89 nodes and 845 edges. Our study indicated that quercetin, beta-sitosterol, luteolin and catechin might be the core ingredients of CSSGF, and EGFR and c-Myc might be the latent therapeutic targets of CSSGF in the treatment of TNBC. GO and KEGG analyses indicated that the anticancer effect of CSSGF on TNBC was mainly associated with DNA binding, transcription factor binding, and other biological processes. The related signaling pathways mainly involved the TNF-a, IL-17, and apoptosis pathways. The molecular docking data indicated that quercetin, beta-sitosterol, luteolin, and catechin had high affinity for EGFR, JUN, Caspase-3 and ESR1, respectively. In vitro, we found that CSSGF could suppress the expression of c-Myc or promote the expression of EGFR. In addition, we found that quercetin downregulates c-Myc expression in two BC cell lines.

Conclusion: This study revealed the effective ingredients and latent molecular mechanism of action of CSSGF against TNBC and confirmed that quercetin could target c-Myc to induce anti-BC effects.

Keywords: c-Myc; chaishao shugan formula; molecular docking; network pharmacology; triple-negative breast cancer.

MeSH terms

Catechin*
ErbB Receptors / genetics
Humans
Luteolin
MCF-7 Cells
Molecular Docking Simulation
Quercetin
Triple Negative Breast Neoplasms* / drug therapy
Triple Negative Breast Neoplasms* / genetics

Substances

Catechin
Luteolin
Quercetin
ErbB Receptors

Grants and funding

This study was financially supported by the Science and Technology Foundation in Guangzhou (2023A04J2147 to TF), Key Research and Development Plan for Science and Technology in Guangzhou(202206080012 to BZ),National Natural Science Foundation of China (82104951 to YYH).