Rutin suppresses enzalutamide-resistant LNCaP prostate cancer cells by regulating epithelial–mesenchymal transition and enhancing mitochondrial biogenesis

Purpose: Managing castration-resistant prostate cancer (CRPC) is a major clinical challenge. Rutin, an antioxidant flavonoid, has promising antitumor properties. Materials and methods: This study aimed to explore the inhibitory effects of rutin on CRPC. LNCaP and LNCaP enzalutamide-resistant (LNCaP Enz-R) cells were treated with various concentrations of rutin for 24 hours. Cell viability and migratory capacity were assessed using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide and wound healing assays. Reactive oxygen species production and mitochondrial biogenesis were measured using ELISA kits. Western blotting and immunofluorescence staining were used to evaluate epithelial–mesenchymal transition (EMT)-related markers and AMPK signaling pathways. Results: Rutin treatment significantly reduced the proliferation and migration of LNCaP and LNCaP Enz-R cells. Furthermore, rutin increased superoxide dismutase activity and promoted mitochondrial biogenesis. Rutin downregulated EMT markers, including Slug, Snail, and α-SMA, and upregulated E-cadherin expression. Moreover, rutin significantly elevated key regulators of mitochondrial homeostasis, such as AMPK, SIRT1, PGC-1α, and NRF1. AMPK activation was involved in modulating α-SMA and E-cadherin expression. Conclusion: Rutin effectively inhibits enzalutamide-resistant prostate cancer cells (LNCaP) by suppressing EMT and enhancing mitochondrial biogenesis. These findings contribute to the growing body of knowledge regarding alternative therapeutic approaches for patients with advanced CRPC by deciphering the impact of rutin on EMT regulation and mitochondrial biogenesis.