Diosgenin inhibits the expression of NEDD4 in prostate cancer cells.

Prostate cancer is the second most common malignancy among men and causes a myriad of health problem for males that are diagnosed with the cancer. Although the 5-year relative survival rate of prostate cancer patients has been significantly increased due to prostate-specific antigen testing and treatment advances, patients that develop metastatic castrate-resistant prostate cancer continue to have poor survival rates. Thus, it is critical to discover new therapeutics to treat prostate cancer. Diosgenin is a steroidal saponin from Trigonella foenum graecum, which has been previously identified to exert anti-tumor properties. Neural precursor cell expressed developmentally down-regulated protein 4 (NEDD4) is an E3 ligase that degrades multiple different proteins, and plays an oncogenic role in human cancer. In this study, we explore the molecular mechanism by which diosgenin mediates anti-tumor effects in prostate cancer cells. We found that diosgenin treatment led to cell growth inhibition, apoptosis and cell cycle arrest. Notably, we found that diosgenin inhibited the expression of NEDD4 in prostate cancer cells. Furthermore, overexpression of NEDD4 overcame the diosgenin-mediated anti-tumor activity, while downregulation of NEDD4 promoted the diosgenin-induced anti-cancer function in prostate cancer cells. Our findings indicate that diosgenin is a potential new inhibitor of NEDD4 in prostate cancer cells.