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

La apigenina modula la comunicación cruzada estromal-epitelial asociada al envejecimiento en las células de la próstata

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.

Resumen

Antecedentes: El potencial terapéutico de los fitonutrientes ha ganado una atención significativa debido a sus propiedades bioactivas y su eficacia en el manejo de enfermedades, incluidos los cánceres. La apigenina, una flavona abundante en frutas y verduras, es conocida por sus efectos antiinflamatorios, antioxidantes y anticancerígenos. Métodos: En este estudio, investigamos el potencial mejorador de la apigenina en la proliferación aberrante de células epiteliales de próstata normales, impulsada por los factores paracrinos de origen estromal, cuando se acondicionó con estradiol (20 pM) y dihidrotestosterona (10 nM). Resultados: La apigenina (5 µM) inhibió significativamente la proliferación aberrante de células epiteliales, tanto en condiciones de aislamiento como en condiciones de co-cultivo estromal. En particular, el tratamiento redujo el tamaño de los esferoides y los patrones de ramificación en los modelos de cultivo de superposición tridimensional (3D). La tinción de células vivas con Calcein acetoxymethyl ester (Calcein AM) reveló una marcada disminución en el número de células viables después del tratamiento. Además, la apigenina aumentó la expresión del receptor de estrógeno beta (ERβ), un supresor tumoral reconocido, e indujo la apoptosis, al tiempo que inhibía la proliferación de células del estroma. Conclusiones: Estos resultados brindan información valiosa sobre el potencial preventivo de la apigenina contra las patologías de próstata impulsadas por interacciones estromales-epiteliales, lo que ofrece una base para futuras investigaciones sobre estrategias dietéticas para la prevención del cáncer.

Apigenin; Prostate; Stromal-epithelial interaction; Sex-steroids (Estrogen, DHT); Endocrine cancers

Palabras Clave

Apigenina; Próstata; Interacción estromal-epitelial; Esteroides sexuales (estrógeno, DHT); Cánceres endocrinos

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