We found that diosgenin treatment inhibited cell growth in a dose-dependent manner (Figure 1A)
July 18, 2021
We found that diosgenin treatment inhibited cell growth in a dose-dependent manner (Figure 1A). 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. Keywords: NEDD4, prostate cancer, diosgenin, growth, invasion Introduction Among men worldwide, prostate cancer is the second leading cancer diagnosis and causes a significant public health problem . Almost 1.3 million new cases of prostate cancer and 358,989 deaths are projected to occur globally . In addition, 164,690 new cases of prostate cancer were projected to be diagnosed in the United States in 2018, which would make it the most common cancer type affecting males in the United States . This year, 29,430 deaths from prostate cancer are expected to occur in the United States, which among men is second only behind to lung cancer . Earlier diagnoses due to widespread PSA (prostate specific antigen) testing combined with treatment advances have contributed to a significant increase in the 5-year relative survival rate of prostate cancer patients . Currently, the therapeutic JIB-04 strategy for prostate cancer includes surgery, radiation, chemotherapy, and hormonal ablation therapy . However, patients with prostate cancer can develop mCRPC (metastatic castrate-resistant prostate cancer) due to androgen deprivation treatment resistance, which has poor survival rates . Therefore, it is necessary to identify new therapeutics to treat prostate cancer. Diosgenin is a steroidal saponin that is commonly isolated from Trigonella foenum graecum, and has been identified to exert multiple anti-tumor properties . For example, diosgenin inhibits cell proliferation, and induces apoptosis, and causes cell cycle arrest. Mechanistically, diosgenin upregulates p53 and caspase-3 activity, and it releases apoptosis inducing factor (AIF) in human cancer cells . Studies also show that diosgenin treatment leads to cell cycle arrest and apoptosis due to activation of cPLA2 (calcium-sensitive cytosolic phospholipase A2) and COX-2 (cyclooxygenase-2) overexpression in erythroleukemia cells [8,9]. Moreover, the effect of diosgenin on breast cancer cells was evaluated in an electrochemical study, which revealed that diosgenin effectively inhibits viability and proliferation . Diosgenin also inhibits pAkt expression and Akt kinase activity, which subsequently downregulates downstream Akt targets, JIB-04 such as NF-B (nuclear factor kappaB), Bcl-2 (B-cell lymphoma 2), Survivin and XIAP (X-linked inhibitor of apoptosis protein) in breast cancer cells . Diosgenin induces apoptosis due to HMG (3-hydroxy-3-methylglutaryl) CoA suppression in human colon carcinoma cells . In these same cells, diosgenin induces apoptosis via COX-2 (cyclooxygenase 2) and LOX-5 (5-lipoxygenase) regulation . Diosgenin also inhibits cell proliferation through autophagy and apoptosis cascades that are downstream of PI3K (phosphoinositide 3-kinase)/Akt/mTOR (mammalian target of rapamycin complex) inhibition in prostate cancer cells . Furthermore, diosgenin retards cell migration and invasion by reducing Rabbit Polyclonal to PRIM1 the expression of MMP-2 (matrix metalloproteinase-2) and MMP-9 in prostate cancer cells . Although prior reports have identified a function for diosgenin in human cancer cells, including prostate cancer cells, the underlying molecular mechanisms have not been fully elucidated. In the current study, we explored the molecular basis of diosgenin-mediated JIB-04 tumor suppression in prostate cancer cells. We found that diosgenin exposure induced cell growth inhibition, apoptosis, and cell cycle arrest. Moreover, we found that the expression of NEDD4 in prostate cancer cells was inhibited by diosgenin. Furthermore, overexpression of NEDD4 overcame the anti-tumor activity in prostate cancer cells that was mediated by diosgenin. NEDD4 downregulation promoted diosgenin-induced anti-cancer effects. Our findings indicate that diosgenin could be a new therapeutic inhibitor JIB-04 of NEDD4 in prostate cancer cells. Materials.