The Flavonoid Apigenin Is a Progesterone Receptor Modulator with In Vivo Activity in the Uterus

Area of Science:

• Endocrinology
• Molecular Biology
• Pharmacology

Background:

• Apigenin, a flavonoid, possesses known anti-cancer properties, but its precise mechanisms remain elusive.
• Previous research suggests apigenin may function as a phytoprogestin, a natural compound interacting with the progesterone receptor (PR).

Purpose of the Study:

• To investigate apigenin's interaction with the progesterone receptor (PR).
• To characterize its in vitro and in vivo progestin-like effects.
• To elucidate its anti-cancer mechanisms related to PR signaling.

Main Methods:

• Molecular docking simulations to assess apigenin-PR binding affinity.
• In vitro assays using Ishikawa and T47D cells to measure PR activity and cell proliferation.
• Western blot analysis to detect PR degradation.
• In vivo studies in animal models to evaluate uterine effects.

Main Results:

• Molecular docking indicated apigenin binds to PR, albeit with lower affinity than progesterone.
• Apigenin demonstrated mixed agonist activity, increasing PR activity in PR-expressing cells and inhibiting it in the presence of progesterone.
• Apigenin induced PR degradation and reduced proliferation in Ishikawa cells via a PR-independent pathway.
• In vivo, apigenin counteracted genistein-induced uterine proliferation and altered endometrial gene expression.

Conclusions:

• Apigenin is confirmed as a phytoprogestin with mixed agonist properties.
• Apigenin exhibits in vivo efficacy by modulating PR activity and inhibiting estrogen receptor-mediated uterine proliferation.
• These findings provide insights into apigenin's potential as a therapeutic agent targeting hormone-dependent conditions.