Apigenin modulates aging-associated stromal-epithelial cross-talk in prostate cells

Background: The therapeutic potential of phytonutrients has gained significant attention due to their bioactive properties and effectiveness in disease management, including cancers. Apigenin, a flavone abundant in fruits and vegetables is known for its anti-inflammatory, antioxidant and anti-cancer effects. Methods: In this study, we investigated the ameliorative potential of apigenin on aberrant proliferation of normal prostate epithelial cells, driven by the paracrine factors of stromal origin, when conditioned with estradiol (20 pM) and dihydrotestosterone (10 nM). Results: Apigenin (5 µM) significantly inhibited the aberrant epithelial cell proliferation, both in isolation as well as in stromal co-culture conditions. Notably, the treatment reduced spheroid size and branching patterns three-dimensional (3D) overlay culture models. Live cell staining with Calcein acetoxymethyl ester (Calcein AM) revealed a marked decrease in viable cell numbers following treatment. Additionally, apigenin increased the expression of estrogen receptor beta (ERβ), a recognized tumor suppressor and induced apoptosis, while also inhibiting stromal cell proliferation. Conclusions: These results provide valuable insights into the preventive potential of apigenin against prostate pathologies driven by stromal-epithelial interactions, offering a foundation for further research into dietary strategies for cancer prevention.