Potential of Aegle marmelos (L.) Corrêa extracts in the management of breast cancer: Phytochemical profiling and molecular docking studies

Background

Breast cancer is the most prevalent cancer among women and a leading cause of cancer-related fatalities worldwide. Addressing the ongoing challenges of drug resistance, alongside the need for effective, affordable prevention and treatment strategies, is essential for reducing its impact.

Objective

This study evaluates the anticancer potential of Aegle marmelos (L.) Corrêa leaf extracts through in vitro assays and in silico molecular studies.

Methods

Hexane, methanol, and aqueous extracts of Aegle marmelos (L.) Corrêa leaves were screened for phytochemical composition. Antioxidant potential was assessed using the DPPH assay, while anticancer activity against MCF-7 breast cancer cells was evaluated using the MTT assay. The most potent extract underwent GC-MS and LC-MS analyses to identify bioactive compounds. Selected phytochemicals were subjected to molecular docking studies against Human Estrogen Alpha receptor (PDB ID: 3ERT) and Epidermal Growth Factor Receptor (PDB ID: 2J5F), followed by molecular dynamics simulations to assess complex stability. Toxicity predictions were conducted to evaluate the safety profile of lead compounds.

Results

Phytochemical analysis confirmed the presence of bioactive compounds, including flavonoids, phenols, and phytosterols. The methanol extract showed strong antioxidant activity (IC50:31.82 ± 0.46 µg/mL), while the hexane extract demonstrated significant cytotoxicity against MCF-7 cells (IC50:24.27 ± 2.39 µg/mL). GC-MS and LC-MS analyses identified 22 bioactive compounds, among which Caryophyllene oxide emerged as a promising therapeutic candidate due to its strong binding affinity for both Human Estrogen Alpha receptor (PDB ID: 3ERT) and Epidermal Growth Factor Receptor (PDB ID: 2J5F). Molecular dynamics simulations confirmed its stable interactions, and toxicity assessments indicated a favorable safety profile, reinforcing its potential for breast cancer treatment.

Conclusion

These findings highlight the potential of Aegle marmelos (L.) Corrêa leaf extracts as a natural anticancer agent, with Caryophyllene oxide emerging as a promising lead compound due to its strong binding affinity, stability, and favorable safety profile. This study provides a foundation for further preclinical and clinical investigations to explore its therapeutic potential for breast cancer treatment.