Exploring honey-derived compounds as potential inhibitors of NDRG1 for breast cancer treatment under hypoxic conditions: a multiomics profiling, molecular docking, and molecular dynamics study

Abstract Background Hypoxia has been recognized as a major contributor to cancer progression. Targeting hypoxia-derived factors, particularly in breast cancer, may present an auspicious strategy for cancer therapy. Honey-derived natural products have demonstrated therapeutic potential for various ailments, including cancer. However, research on their effects under hypoxic conditions remains limited. This study aims to elucidate the potential of honey-derived natural products as anticancer agents for breast cancer under hypoxic conditions. An integrative bioinformatics approach was employed, including drug-likeness screening, toxicity analysis, differential gene expression analysis, gene and protein enrichment analysis, immune infiltration correlation analysis, molecular docking, and molecular dynamic simulations. Results Five potential compounds with favorable drug-like properties and minimal toxicity effects were identified, including 2,2-dimethyl-8-prenylchromene, chrysin, galangin, kaempferol, and pinobanksin. These compounds were further assessed for their ability to target hypoxia-associated factors. Public database analysis revealed that N-myc downregulated gene-1 (NDRG1) is significantly upregulated in breast cancer under hypoxic conditions. Enrichment analysis demonstrated that elevated NDRG1 expression is strongly associated with poor patient outcomes. Interestingly, high NDRG1 expression is correlated with immune cell infiltration, including monocytes, myeloid-derived suppressor cells, and neutrophils, which are known components of the tumor microenvironment that promote cancer progression. Molecular docking results indicated that chrysin exhibited a more favorable binding affinity than other compounds, including the control drug Combretastatin A-4. Moreover, a 100-ns molecular dynamics simulation demonstrated that chrysin exhibited dynamic behavior comparable to the control drug across nearly all measured parameters, suggesting its potential as an anticancer agent. Conclusion These findings highlight the promise of chrysin as a candidate for breast cancer treatment under hypoxic conditions by targeting NDRG1. Further experimental validation is warranted to support its development as a therapeutic agent.