Pulsatilla Saponin D Suppresses Proliferation and Induces Apoptosis in Human Prostatic Cells

The growing global aging population is contributing to an increasing burden of benign prostatic hyperplasia (BPH), highlighting the need for novel, highly effective and low-toxicity therapies. In light of its well-documented anti-inflammatory and anti-tumor properties, we investigated the potential of the natural product Pulsatilla saponin D (PSD) in treating BPH. For the first time, we demonstrate that PSD significantly inhibits the proliferation of and induces apoptosis in the immortalized human normal prostatic stromal cell line, human prostate fibroblasts, and the human benign prostatic hyperplasia epithelial cell line. Mechanistic studies involving transcriptome analysis and RT-qPCR validation revealed that PSD likely exerts its effects by downregulating the expression of the androgen receptor and by modulating multiple signaling pathways synergistically, including the Phosphatidylinositol 3-kinase/Protein Kinase B, Tumor Necrosis Factor, Hypoxia-Inducible Factor-1 and Interleukin-17 pathways.