title: Snail-mediated regulation of reactive oxygen species in ARCaP human prostate cancer cells.
abstract: Reactive oxygen species increases in various diseases including cancer and has been associated with induction of epithelial-mesenchymal transition (EMT), as evidenced by decrease in cell adhesion-associated molecules like E-cadherin, and increase in mesenchymal markers like vimentin. We investigated the molecular mechanisms by which Snail transcription factor, an inducer of EMT, promotes tumor aggressiveness utilizing ARCaP prostate cancer cell line. An EMT model created by Snail overexpression in ARCaP cells was associated with decreased E-cadherin and increased vimentin. Moreover, Snail-expressing cells displayed increased concentration of reactive oxygen species (ROS), specifically, superoxide and hydrogen peroxide, in vitro and in vivo. Real Time PCR profiling demonstrated increased expression of oxidative stress-responsive genes, such as aldehyde oxidase I, in response to Snail. The ROS scavenger, N-acetyl cysteine partially reversed Snail-mediated EMT after 7 days characterized by increased E-cadherin levels and decreased ERK activity, while treatment with the MEK inhibitor, UO126, resulted in a more marked effect by 3 days, characterized by cells returning back to the epithelial morphology and increased E-cadherin. In conclusion, this study shows for the first time that Snail transcription factor can regulate oxidative stress enzymes and increase ROS-mediated EMT regulated in part by ERK activation. Therefore, Snail may be an attractive molecule for therapeutic targeting to prevent tumor progression in human prostate cancer.
authors.affiliation: Center for Cancer Research and Therapeutic Development, Department of Biological Sciences, Clark Atlanta University, Atlanta, GA 30314, USA.
authors.forename: Petrina
authors.initials: P
authors.lastname: Barnett
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Arnold
authors.forename: Roman
authors.initials: R
authors.lastname: Mezencev
authors.forename: Leland W K
authors.initials: LW
authors.lastname: Chung
authors.forename: Majd
authors.initials: M
authors.lastname: Zayzafoon
authors.forename: Valerie
authors.initials: V
authors.lastname: Odero-Marah
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D018384:Oxidative Stress / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D017382:Reactive Oxygen Species; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors