Phillyrin Modulates AMPK-Associated Cellular Responses and Migration in PC3 Prostate Cancer Cells

Males with prostate cancer exhibit substantial mortality and metastasis; however, few effective treatment strategies are available for advanced prostate cancer. Phillyrins (PHNs) are lignan glycosides that have been reported to exhibit diverse biological activities, including potential anticancer effects. We aimed (1) to assess the effect of PHN on PC3 prostate cancer cells and (2) to examine cellular responses associated with its activity. To assess the effects of PHN, it was exposed to various concentrations of PHN (1, 2.5, and 5 μM) for 24 h. A wound-healing assay was performed to evaluate cell migration. Western blotting and immunofluorescence were used to investigate the expression of adenosine monophosphate-activated protein kinase (AMPK)-associated proteins and transcription factors involved in epithelial-mesenchymal transition (EMT). PHN exposure was associated with reduced migratory capacity of PC3 cells under noncytotoxic conditions. PHN exposure was associated with decreased α-smooth muscle actin, Snail, and Slug expression while increasing E-cadherin expression. Sirtuin 1 (SIRT1) and nuclear respiratory factor 1 (NRF1) protein levels were upregulated in PHN-treated cells, accompanied by changes in AMPK protein expression. Pharmacological inhibition with Compound C attenuated PHN-associated changes in EMT-related marker expression in PC3 cells. Thus, PHN exposure may influence EMT-associated phenotypes in PC3 cells, potentially involving AMPK-associated signaling.