cytochrome-c-t and psoralidin

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

Topics: Acetylcysteine; Antioxidants; Apoptosis; Benzofurans; beta Catenin; Cadherins; Caspase 3; Caspase 9; Catalase; Cell Line, Tumor; Cell Movement; Cell Proliferation; Coumarins; Cytochromes c; Enzyme Activation; Epithelial-Mesenchymal Transition; Humans; Male; Membrane Potential, Mitochondrial; Neoplasm Invasiveness; Oxidative Stress; Poly(ADP-ribose) Polymerases; Prostatic Neoplasms; Reactive Oxygen Species; Snail Family Transcription Factors; Superoxide Dismutase; Superoxide Dismutase-1; Transcription Factors; Transcription, Genetic