Curcumin and its nano-formulations: Defining triple-negative breast cancer targets through network pharmacology, molecular docking, and experimental verification

Abstract

Background: Curcumin (CUR) displays the capability of suppressing the proliferation and metastasis of various cancer cells. However, the effects and underline mechanisms of CUR to treat triple-negative breast cancer (TNBC) have not been systematically elucidated with an appropriate method.Methods: In the present research, a combination method of network pharmacology, molecular docking, and in vitro bio-experiment was used to investigate the pharmacological actions and underline mechanisms of CUR against TNBC. First, common targets of CUR and TNBC were screened via Venny 2.1.0 after potential CUR-related targets and targets of TNBC were got from several public databases. Then, the Gene Ontology (GO) function and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed on the Metascape website, and the network of compound-targets-pathways was constructed via Cytoscape software. Moreover, the network of protein-protein interaction was constructed by the STRING database to screen potential targets. Moreover, molecular docking was applied to affirm the interaction of CUR with the screened top 10 potential targets. Finally, in vitro experiments were used to further verify the effects and mechanisms of CUR and its nano-formulation (CUR-NPs) against TNBC.Results: Forty potential targets of CUR against TNBC were obtained. STAT3, AKT1, TNF, PTGS2, MMP9, EGFR, PPARG, NFE2L2, EP300, and GSK3B were identified as the top 10 targets of CUR against TNBC. In vitro experiment verified that CUR and CUR-NPs could not only restrain the invasion, migration, and proliferation of MDA-MB-231 cells but also induce their apoptosis. In addition, molecular docking demonstrated that CUR could bind spontaneously with the screened top 10 targeted proteins, and a real-time PCR experiment demonstrated that both CUR and CUR-NPs could downregulate the genetic expression levels of the 10 targets. Moreover, according to the CUR-targets-pathways network, PI3K-Akt, EGFR tyrosine kinase inhibitor resistance, JAK-STAT, Foxo, and HIF-1 signaling pathways were identified as the important pathways of CUR effects on TNBC. Among them, the inhibiting effects of CUR and CUR-NPs on the JAK-STAT signaling pathway were further verified by the western blot analysis.Conclusion: Taken together, the present research demonstrates that CUR and CUR-NPs have pharmacological effects against TNBC via a multi-target and multi-pathway manner.

The therapeutic and prognostic role of cuproptosis-related genes in triple negative breast cancer

“…Some of the important findings are as follows. NFE2L2 was identified as one of top 10 targets of Curcumin against TNBC [ 22 ]. NLRP3 may mediate the cisplatin induced pyroptosis via activation in TNBC (via activation of MEG3/NLRP3/caspase-1/GSDMD pathway) [ 23 ].…”

maGENEgerZ: An Efficient AI-Based Framework Can Extract More Expressed Genes and Biological Insights Underlying Breast Cancer Drug Response Mechanism

“…These results demonstrate the importance of these TFs and can aim in developing therapeutic strategies for breast cancer treatment. Thirteen genes (AKT1, ARAF, CCND1, EGFR, ERBB2, ERBB3, MTOR, IGF1R, JAK2, MET, PTEN, RAF1, and STAT3) were related to EGFR tyrosine kinase inhibitor resistance (WP4806), which was reported as significant pathway associated with breast cancer [69,84]. Twelve genes (AKT1, CCND1, ERBB2, ESR1, MTOR, IRS1, JAK2, NOS3, PTEN, RAF1, STAT1, and STAT3) were linked to Leptin signaling pathway (WP2034), reported to have a key role in breast cancer tumorigenesis [85].…”

Curcumin suppresses metastasis of triple-negative breast cancer cells by modulating EMT signaling pathways: An integrated study of bioinformatics analysis

“…Although previous studies have demonstrated curcumin’s capacity to inhibit cell proliferation and invasion in human TNBC MDA-MB-231 cells, [19] the underlying molecular mechanisms are still being explored. This study seeks to bridge this gap in knowledge by employing both bioinformatics and experimental approaches to investigate the effects of curcumin on cell motility in TNBC cell lines, specifically Hs578T and MDA-MB-231 cells.…”

“…[13,14] Thus, curcumin may play a significant role in the initiation and progression of various cancers, including breast, lung, and liver cancers, through affecting multiple signaling and molecular pathways, such as Rb, P53, mitogen-activated protein kinase, phosphatidylinositol 3-K (PI3K)/protein kinase B, and NF-kappaB (nuclear factor kappa B cells, NF-κB). [15][16][17][18] Although previous studies have demonstrated curcumin's capacity to inhibit cell proliferation and invasion in human TNBC MDA-MB-231 cells, [19] the underlying molecular mechanisms are still being explored. This study seeks to bridge this gap in knowledge by employing both bioinformatics and experimental approaches to investigate the effects of curcumin on cell motility in TNBC cell lines, specifically Hs578T and MDA-MB-231 cells.…”