Prostate cancer is a highly prevalent malignancy in men, with epithelial–mesenchymal transition (EMT) playing a critical role in cancer progression and metastasis. Salvianolic acid (SA), a polyphenolic compound derived from Salvia miltiorrhiza, has exhibited potential anticancer effects. This study investigated the role of SA in regulating EMT and mitochondrial biogenesis in LNCaP and LNCap-Enz prostate cancer cells.

The effects of SA on cell viability, proliferation, migration, and mitochondrial function were evaluated using the 4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, wound healing assay, and JC-1 staining. The expression of EMT-related markers (E-cadherin, smooth muscle actin (SMA), Snail, and Slug) and mitochondrial biogenesis-related pathways AMP-activated protein kinase (AMPK), SIRT1, PGC-1α, and NRF1) were analyzed by western blot. ATP production and mitochondrial membrane potential (ΔΨm) were measured to evaluate mitochondrial activity.

SA significantly suppressed the viability, proliferation, and migration of LNCaP and LNCaP-Enz cells. EMT was inhibited, as evidenced by the upregulation of E-cadherin and the downregulation of SMA, Snail, and Slug. SA treatment also enhanced mitochondrial biogenesis through the activation of the AMPK, SIRT1, PGC-1α, and NRF1 signaling pathways, leading to increased ATP production and ΔΨm.

SA exerted anticancer effects in prostate cancer cells by inhibiting EMT and activating mitochondrial biogenesis. These findings indicate the potential of SA as a therapeutic agent for prostate cancer.