Differentially expressed gene profile and relevant pathways of the traditional Chinese medicine cinobufotalin on MCF‑7 breast cancer cells

Abstract

Cinobufotalin is a chemical compound extracted from the skin of dried bufo toads that may have curative potential for certain malignancies through different mechanisms; however, these mechanisms remain unexplored in breast cancer. The aim of the present study was to investigate the antitumor mechanism of cinobufotalin in breast cancer by using microarray data and in silico analysis. The microarray data set GSE85871, in which cinobufotalin exerted influences on the MCF-7 breast cancer cells, was acquired from the Gene Expression Omnibus database, and the differentially expressed genes (DEGs) were analyzed. Subsequently, protein interaction analysis was conducted, which clarified the clinical significance of core genes, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used to analyze cinobufotalin-related pathways. The Connectivity Map (CMAP) database was used to select existing compounds that exhibited curative properties similar to those of cinobufotalin. A total of 1,237 DEGs were identified from breast cancer cells that were treated with cinobufotalin. Two core genes, SRC proto-oncogene non-receptor tyrosine kinase and cyclin-dependent kinase inhibitor 2A, were identified as serving a vital role in the onset and development of breast cancer, and their expression levels were markedly reduced following cinobufotalin treatment as detected by the microarray of GSE85871. It also was revealed that the ‘neuroactive ligand-receptor interaction’ and ‘calcium signaling’ pathways may be crucial for cinobufotalin to perform its functions in breast cancer. Conducting a matching search in CMAP, miconazole and cinobufotalin were indicated to possessed similar molecular mechanisms. In conclusion, cinobufotalin may serve as an effective compound for the treatment of a subtype of breast cancer that is triple positive for the presence of estrogen, progesterone and human epidermal growth factor receptor-2 receptors, and its mechanism may be related to different pathways. In addition, cinobufotalin is likely to exert its antitumor influences in a similar way as miconazole in MCF-7 cells.

The Potential Mechanisms of Cinobufotalin Treating Colon Adenocarcinoma by Network Pharmacology

“…Cinobufotalin was previously found to inhibit the activity of Na + /K + -ATP enzyme ( Akimova et al, 2005 ). In addition, cinobufotalin has inhibitory effects on many tumors, including lung, liver, ovarian, breast, and gastric cancers ( Kai et al, 2014 ; Cheng et al, 2015 ; Afroze et al, 2018 ; Li J. et al, 2019 ; Sun et al, 2019 ). More importantly, cinobufotalin also alters the sensitivity of chemotherapeutic drugs ( Li Y. et al, 2019 ; Liu et al, 2022 ).…”

Development and validation of a necroptosis-related gene prognostic score to predict prognosis and efficiency of immunotherapy in gastric cancer

“…Moreover, NRGPS could independently predict the OS for GC patients. We used the GSEA analysis to investigate the gene sets enriched in the two NRGPS groups in order to more thoroughly examine the function of these three marker genes in GC, and the results showed that the gene sets of the high-NRGPS group were mainly enriched in the "Neuroactive ligand-receptor interaction", "Calcium signaling pathway", "Vascular smooth muscle contraction", and "Focal adhesion", which are associated with tumor development (24)(25)(26)(27).…”

Potential Diagnostic and Prognostic Utility of miR-141, miR-181b1, and miR-23b in Breast Cancer

“…The hub genes in module 2 were significantly associated with neuroactive ligand–receptor interaction, pathways in cancer, and Ras-proximate-1 or Ras-related protein 1 (Rap1) signaling pathways. The neuroactive ligand–receptor interaction pathway involves many G-protein-coupled receptors and is one of the most common dysregulated pathways of malignancies, including breast cancer [ 57 ]. Rap1 is a small G protein that regulates diverse processes such as cell adhesion, cell–cell junction formation, and cell polarity, which are critical for cellular migration, invasion, and metastasis [ 58 , 59 ].…”