Molecular docking prediction and in vitro studies elucidate anti-cancer activity of phytoestrogens

Area of Science:

• Biochemistry
• Molecular Biology
• Pharmacology

Background:

• Dietary phytoestrogens, like genistein and daidzein, are plant-derived compounds with potential health benefits.
• Estrogen receptor-positive (MCF-7) and estrogen receptor-negative (MDA-MB-231) breast cancer cells are common models for studying cancer therapies.

Purpose of the Study:

• To evaluate the chemosensitization and apoptotic effects of aglycone-rich phytoestrogen extracts from soybean and flaxseed on breast cancer cells.
• To investigate the molecular mechanisms underlying the observed effects using in silico and gene expression analyses.

Main Methods:

• Chemosensitization was assessed using MTT assays.
• Apoptosis was measured via activated caspase-3/7 activity using flow cytometry and Western blotting.
• In silico molecular docking (PharmMapper, Schrödinger) and gene/protein expression studies (qPCR, Western blot) were performed.

Main Results:

• Phytoestrogen extracts demonstrated significant apoptotic activity and chemosensitization in both MCF-7 and MDA-MB-231 cells.
• Molecular docking identified aldose reductase (AKR1B1), Harvey rat sarcoma (HRAS), and glutathione S-transferase pi (GSTP1) as potential targets for genistein, daidzein, and secoisolariciresinol, respectively.
• Gene and protein expression studies confirmed the down-regulation of AKR1B1, HRAS, and GSTP1 by the phytoestrogen extracts.

Conclusions:

• The study confirms the chemosensitization and apoptotic potential of dietary phytoestrogens in breast cancer cells.
• Computational and experimental data suggest that genistein, daidzein, and secoisolariciresinol are promising candidates for developing novel inhibitors targeting AKR1B1, HRAS, and GSTP1, respectively.
• These findings support further medicinal chemistry optimization for potential therapeutic applications.