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Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a transcription factor and it contributes to breast cancer growth and metastasis. Hence, NF-κB is considered as a target for anti-breast cancer drugs. NF-κB was retrieved from the UniProtKB Data Base with UniProt ID P19838, its energy was minimized and subjected to molecular dynamic simulations using Gromacs v5.0.7 software with GROMOS96 43A1 force field implementing the steepest descent algorithm. The structure of genistein was retrieved from NCBI PubChem database in .sdf format and convert to .pdb format. The genistein compound was docked into the active site of NF-κB proteins with AutoDock tools 1.5. The genistein compound displayed the best binding energies at -6.29 (NF-κB) kcal/mol correspondingly. The binding interactions of this compound with the active site of NF-κB proteins suggested that amino acid residues (Lys52, Ser243, Asp274, Lys, 275) might play a key role in anti-breast cancer activity. Genistein also inhibited the translocation and expression of NF-κB in the nucleus of both breast cancer cell lines. These findings might increase our understanding of the molecular and functional role of NF-κB in breast cancer. It could also help in developing additional druggable NF-κB inhibitors with high potency, specificity and outstanding bioavailability.

Background: Genistein being a phytoestrogen imitates the characteristics of estrogen, which can be useful to treat conditions by reducing the estrogen levels at the time of menopause, osteoporosis and high risk for breast cancer. Objective: The superior binding of genistein to ERβ might help in reducing breast malignancy risk. Conclusion: Genistein induces cell cycle arrest, anti-metastatic properties and ultimately affects the breast cancer cell growth by multiple mechanisms. Genistein-mediated anti-proliferative or anti-growth effects are usually observed at higher concentrations. These signaling pathways involve the decrease of NF-κB, HIF-1α, VEGF, and an increase of tumor suppressor p21. This will provide further insight into understanding the biology of transcription factors NF-κB, and HIF-1α in breast cancer.