Nanoparticle-enhanced apigenin suppresses androgen receptor signaling and cellular plasticity in LNCaP cells

Abstract Prostate cancer remains highly dependent on androgen receptor (AR) signaling, yet therapeutic escape often emerges through incomplete suppression of AR-driven transcription and activation of compensatory survival pathways. Here, we investigated whether a hyaluronic acid-coated selenium nanoparticle formulation loaded with apigenin (HA-SeNP-Api) could enhance the anti-tumor activity of apigenin in androgen-responsive LNCaP prostate cancer cells. Selenium nanoparticles were generated by reduction of sodium selenite with ascorbic acid, followed by apigenin loading and hyaluronic acid coating. After 72 h treatment, HA-SeNP-Api produced a consistent biological response across several measured endpoints among the tested groups. Apigenin screening identified 6.25 µM as a biologically active sub-IC50 working concentration. At this dose, the nanoformulation reduced AR and PSA mRNA expression to 0.27-fold and 0.42-fold, respectively, and lowered PSA protein to 10% of control. Total apoptosis increased to 44.30%, compared with 31.36% for selenium nanoparticles alone, 9.77% for apigenin, and 3.70% for enzalutamide. The formulation also increased p53 and p21 expression, reduced SOX2, OCT3/4 and SLUG, and retained growth-inhibitory activity in 3D spheroids. These findings suggest that HA-SeNP-Api enhances the biological activity of apigenin under the tested in vitro conditions and modulates AR/PSA-associated readouts, apoptosis-associated responses, and selected plasticity-associated transcripts in LNCaP cells.