Systems pharmacology in combination with proteomics reveals underlying mechanisms of Xihuang pill against triple-negative breast cancer

Abstract

Xihuang pill (XHP), a traditional Chinese herbal formula, has been clinically used as an adjuvant therapy against triple-negative breast cancer (TNBC) via inhibiting cancer cell invasion and proliferation, as well as promoting cancer cell apoptosis. However, its anti-TNBC bio-active ingredients and possible mechanisms are still unclear. Herein, the hub bioactive compounds and underlying mechanisms of XHP against TNBC were systematically elucidated by integrating systems pharmacology approach and in vitro proteomics analysis. Using systems pharmacology analysis and molecular docking evaluation, 28 bio-active compounds and 10 potential therapeutic targets of XHP were identified. Functional analysis showed that the core therapeutic targets against TNBC were mainly involved in epidermal growth factor receptor (EGFR)-phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway to prevent cancer cell proliferation and angiogenesis, as well as to enhance cancer cell apoptosis. The in vitro proteomics analysis identified 153 differentially expressed proteins (DEPs), including HASP90AA1, AKT1, and EGFR, which were also identified as therapeutic targets against TNBC through systems pharmacology analysis. Protein function analysis showed that the DEPs were mainly involved in PI3K-AKT signaling pathway, which was consistent with the result of systems pharmacology, suggesting the reliability of systems pharmacology analysis. Taken together, these findings uncover the underlying mechanism of XHP against TNBC, and provide a scientific method for the rational development of traditional Chinese medicine.

Exploring the Pharmacological Mechanisms of Xihuang Pills Against Prostate Cancer via Integrating Network Pharmacology and Experimental Validation In Vitro and In Vivo

“…The whole prescription is composed of calculus bovis, musk, frankincense, and myrrh. It is commonly applied in the prevention and treatment of breast cancer, cervical cancer, and other tumors ( Wu et al, 2020 ; Xu X et al, 2020 ), but its effect on prostate cancer and exact mechanism are unclear.…”

“…Furthermore, it is recorded that it can be applied in malignant diseases such as Shi-ju, Ru-yan, and E-he. Nowaday, XHP have been used in the treatment of various cancers, such as breast cancer, lung cancer, lymphoma, and so on, and have achieved certain efficacy ( Fu et al, 2020 ; Li et al, 2020 ; Xu X et al, 2020 ). The antitumor mechanism of XHP is via inducing tumor cell apoptosis ( Su et al, 2018 ), inhibiting tumor cell proliferation ( Hao et al, 2018 ), blocking the cell cycle, and regulating tumor microenvironment ( Yang et al, 2020 ), etc.…”

Identification of significant genes and therapeutic agents for breast cancer by integrated genomics

“…Compared to previous studies [61][62][63], we conducted an analysis combining genomic data with drug database analysis to identify novel candidate therapeutic agents for breast cancer treatment. Our study demonstrates the usefulness of this approach for evaluating the relationship among genes, diseases, and drugs.…”

Traditional Chinese Medicine Xihuang Wan Inhibited Lewis Lung Carcinoma in a Syngeneic Model, Equivalent to Cytotoxic Chemotherapy, by Altering Multiple Signaling Pathways

“…A systems pharmacology and proteomics study of XHW on triple-negative breast cancer (TNBC) showed that XHW may be effective on non-small cell lung cancer and small cell lung cancer, as demonstrated by the KEGG signaling pathway enrichment analysis (52).…”