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Induction of reactive oxygen species generation inhibits epithelial–mesenchymal transition and promotes growth arrest in prostate cancer cells
Author(s) -
Das Trinath P.,
Suman Suman,
Damodaran Chendil
Publication year - 2014
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22014
Subject(s) - reactive oxygen species , biology , sod2 , mitochondrial ros , apoptosis , cancer cell , catalase , epithelial–mesenchymal transition , oxidative stress , microbiology and biotechnology , poly adp ribose polymerase , superoxide dismutase , cancer research , biochemistry , metastasis , cancer , enzyme , polymerase , genetics
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. © 2013 Wiley Periodicals, Inc.