Salvianolic Acid Activates ATP‐Driven Mitochondrial Biogenesis to Suppress the Epithelial–Mesenchymal Transition in LNCaP Prostate Cancer Cells

Background Prostate cancer is among the most frequently identified malignant tumors in men. Epithelial–mesenchymal transition (EMT) serves as a key process driving tumor development and enabling cancer cells to spread to remote tissues. Salvianolic acid (SA), a polyphenolic compound derived from Salvia miltiorrhiza , exhibits potential anticancer effects. This research explores the impact of SA on the regulation of EMT and mitochondrial biogenesis in LNCaP and LNCaP‐Enz‐R prostate cancer cells. Methods The effects of SA on cell viability, migration, and mitochondrial function were assessed using MTT assay, wound healing assay, and JC‐1 staining. Western blotting was conducted to assess the levels of EMT‐related markers (E‐cadherin, Snail, α‐SMA, and Slug) along with critical regulators of mitochondrial biogenesis, such as AMP‐activated protein kinase (AMPK), PGC‐1α, SIRT1, and NRF1. ATP production and mitochondrial membrane potential (ΔΨm) were measured to evaluate mitochondrial activity. Results SA significantly inhibited the expansion, viability, and movement of LNCaP and LNCaP‐Enz‐R cells. SA administration significantly inhibited EMT, as indicated by increased E‐cadherin expression and reduced expression of α‐SMA, Snail, and Slug. Moreover, SA promoted mitochondrial biogenesis by activating the AMPK/PGC‐1 α /SIRT1/NRF1 pathway, resulting in enhanced ATP generation and maintenance of ΔΨm. Conclusion SA exhibited strong anticancer effects in prostate cancer cells by inhibiting EMT and stimulating mitochondrial biogenesis, further interfering with tumor progression. Reportedly, SA can be a promising treatment option for prostate cancer.