Related Experiment Video
Updated: Jul 18, 2025
Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
Published on: March 17, 2016
Structure-Based Multi-Targeted Molecular Docking and Dynamic Simulation of Soybean-Derived Isoflavone Genistin as a
Abd Elmoneim O Elkhalifa1, Eyad Al-Shammari1, Mohammed Kuddus2
1Department of Clinical Nutrition, College of Applied Medical Sciences, University of Ha'il, Ha'il P.O. Box 2440, Saudi Arabia.
Abstract:
Globally, breast cancer (BC), the second-biggest cause of cancer death, occurs due to unregulated cell proliferation leading to metastasis to other parts of the human organ. Recently, the exploration of naturally derived anticancer agents has become popular due to their fewer adverse effects. Among the natural products, soybean is a very well-known legume that contains important bioactive compounds such as diadazine, glycetin, genistein, and genistin. Therefore, keeping its therapeutic potential in mind, multi-targeted molecular docking and simulation studies were conducted to explore the potential role of soybean-derived isoflavone genistin against several breast cancer-signaling proteins (ER-alpha, ER-Beta, collapsin response mediator protein 2, CA 15-3, human epidermal growth factor receptor 2). A comparative study of the genistin-protein docked complex was explored to investigate its potential role in BC. The molecular binding energy (∆G) of the docked complex was calculated along with ADMET properties. The molecular docking score of genistin with ubiquitin-like protein activation complex-a type of Cancer Antigen (CA) 15.3 (PDB ID-2NVU, 5T6P, and 1YX8) showed the highest binding energy, ranging from -9.5 to -7.0 Kcal/mol, respectively. Furthermore, the highest docking scores of the complex were additionally put through molecular dynamics (MD) simulation analysis. MD simulations of the selected complex were performed at 100 ns to study the stability of the genistin-ubiquitin-like protein CA 15.3 complex, which appeared to be quite stable. Additionally, the ADMET study demonstrated that genistin complies with all drug-likeness standards, including Lipinski, Egan, Veber, Ghose, and Muegge. Therefore, based on the results, genistin can be considered as one of the potential drugs for the management and treatment of BC. In addition, the obtained results suggest that genistin could pave the way for new drug discovery to manage breast cancer and has potential in the development of nutraceuticals.
Insights
Soybean-derived genistin shows potential as a breast cancer treatment. Molecular docking and simulations confirm its stability and drug-like properties, suggesting a new avenue for cancer management and nutraceutical development.
Area of Science:
- Biochemistry
- Pharmacology
- Computational Biology
Background:
- Breast cancer (BC) is a leading cause of cancer death globally, driven by uncontrolled cell proliferation and metastasis.
- Naturally derived compounds, particularly from soybeans, are gaining attention for cancer therapy due to fewer adverse effects.
- Soybean isoflavones, including genistin, possess bioactive properties with therapeutic potential.
Purpose of the Study:
- To investigate the potential of soybean-derived genistin as an anticancer agent against breast cancer.
- To explore genistin's interaction with key breast cancer-signaling proteins using multi-targeted molecular docking and simulation.
- To evaluate the binding affinity, stability, and drug-likeness properties of genistin-protein complexes.
Main Methods:
- Multi-targeted molecular docking was performed to assess genistin's binding to breast cancer-related proteins (ER-alpha, ER-Beta, Cripto, CA 15.3, HER2).
- Molecular dynamics (MD) simulations were conducted for 100 ns to evaluate the stability of the genistin-CA 15.3 complex.
- ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicity) properties were calculated to assess drug-likeness using established criteria (Lipinski, Egan, Veber, Ghose, Muegge).
Main Results:
- Genistin exhibited significant binding affinity to Cancer Antigen (CA) 15.3, with binding energies ranging from -9.5 to -7.0 Kcal/mol.
- MD simulations confirmed the stability of the genistin-CA 15.3 complex over 100 ns.
- ADMET analysis indicated that genistin adheres to all standard drug-likeness parameters, suggesting favorable pharmacokinetic properties.
Conclusions:
- Genistin demonstrates considerable potential as a therapeutic agent for breast cancer management.
- The findings support genistin's role in novel drug discovery for breast cancer treatment.
- Genistin may also hold promise for the development of effective nutraceuticals for breast cancer patients.
