Induction of reactive oxygen species generation inhibits epithelial-mesenchymal transition and promotes growth arrest in prostate cancer cells.

摘要: Oxidative stress is one causative factor of the pathogenesis and aggressiveness most cancer types, including prostate (CaP). A moderate increase in reactive oxygen species (ROS) induces cell proliferation whereas excessive amounts ROS promote apoptosis. In this study, we explored pro-oxidant property 3,9-dihydroxy-2-prenylcoumestan (psoralidin [pso]), a dietary agent, on CaP (PC-3 C4-2B) cells. Pso greatly induced generation (more than 20-fold) that resulted growth inhibition Overexpression anti-oxidant enzymes superoxide dismutase 1 (SOD1), SOD2, catalase, or pretreatment with pharmacological inhibitor N-acetylcysteine (NAC) significantly attenuated both pso-mediated Furthermore, pso administration inhibited migratory invasive cells by decreasing transcription β-catenin, slug, which epithelial-mesenchymal transition (EMT), concurrently inducing E-cadherin expression Pso-induced loss mitochondrial membrane potential, cytochrome-c release, activation caspase-3 -9 poly (ADP-ribose) polymerase (PARP), led to On other hand, overexpression anti-oxidants rescued effects These findings suggest increasing threshold intracellular could prevent treat metastasis.