title: Muscadine grape skin extract reverts snail-mediated epithelial mesenchymal transition via superoxide species in human prostate cancer cells.
abstract: BACKGROUND
  Snail transcription factor can induce epithelial-mesenchymal transition (EMT), associated with decreased cell adhesion-associated molecules like E-cadherin, increased mesenchymal markers like vimentin, leading to increased motility, invasion and metastasis. Muscadine grape skin extract (MSKE) has been shown to inhibit prostate cancer cell growth and induce apoptosis without affecting normal prostate epithelial cells. We investigated novel molecular mechanisms by which Snail promotes EMT in prostate cancer cells via Reactive Oxygen Species (ROS) and whether it can be antagonized by MSKE.
  
  
  METHODS
  ARCaP and LNCaP cells overexpressing Snail were utilized to examine levels of reactive oxygen species (ROS), specifically, superoxide, in vitro using Dihydroethidium (DHE) or HydroCy3 dyes. Mitosox staining was performed to determine whether the source of ROS was mitochondrial in origin. We also investigated the effect of Muscadine grape skin extract (MSKE) on EMT marker expression by western blot analysis. Migration and cell viability using MTS proliferation assay was performed following MSKE treatments.
  
  
  RESULTS
  Snail overexpression in ARCaP and LNCaP cells was associated with increased concentration of mitochondrial superoxide, in vitro. Interestingly, MSKE decreased superoxide levels in ARCaP and LNCaP cells. Additionally, MSKE and Superoxide Dismutase (SOD) reverted EMT as evidenced by decreased vimentin levels and re-induction of E-cadherin expression in ARCaP-Snail cells after 3 days, concomitant with reduced cell migration. MSKE also decreased Stat-3 activity in ARCaP-Snail cells.
  
  
  CONCLUSIONS
  This study shows that superoxide species may play a role in Snail transcription factor-mediated EMT. Therefore, therapeutic targeting of Snail with various antioxidants such as MSKE may prove beneficial in abrogating EMT and ROS-mediated tumor progression in human prostate cancer.
authors.forename: Liza J
authors.initials: LJ
authors.lastname: Burton
authors.forename: Petrina
authors.initials: P
authors.lastname: Barnett
authors.forename: Basil
authors.initials: B
authors.lastname: Smith
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Arnold
authors.forename: Tamaro
authors.initials: T
authors.lastname: Hudson
authors.forename: Kousik
authors.initials: K
authors.lastname: Kundu
authors.forename: Niren
authors.initials: N
authors.lastname: Murthy
authors.affiliation: Center for Cancer Research and Therapeutic Development, Department of Biological Sciences, Clark Atlanta University, 223 James P Brawley Dr SW, 30314 Atlanta, GA, USA. vodero_marah@cau.edu.
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Odero-Marah
mesh_terms: D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D006801:Humans; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000071250:Snail Family Transcription Factors; D013481:Superoxides / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D027843:Vitis / Q000737:chemistry*
chemical_list: D010936:Plant Extracts; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D013481:Superoxides