Abstract
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.