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Title: Oxidative stress adaptation in aggressive prostate cancer may be counteracted by the reduction of glutathione reductase
Authors: Freitas, Mariana 
Baldeiras, Inês 
Proença, Teresa 
Alves, Vera 
Mota-Pinto, Anabela 
Sarmento-Ribeiro, Ana Bela 
Keywords: Stresse Oxidativo; Cancro da próstata
Issue Date: 2012
Serial title, monograph or event: FEBS Open Bio
Volume: 2
Abstract: Oxidative stress has been associated with prostate cancer development and progression due to an increase of reactive oxygen species (ROS). However, the mechanisms whereby ROS and the antioxidant system participate in cancer progression remain unclear. In order to clarify the influence of oxidative stress in prostate cancer progression, we performed this study in two human prostate cancer cell lines, PC3 and HPV10 (from metastasis and from localized cancer, respectively) and RWPE1 cells derived from normal prostate epithelium. Cells were treated with hydrogen peroxide (H2O2) and PC3 cells were also treated with diethyl maleate (DEM). The effect on cell growth, viability, mitochondria membrane potential and oxidative stress was analysed. Oxidative stress was evaluated based on ROS production, oxidative lesion of lipids (MDA) and on determination of antioxidants, including enzyme activity of glutathione peroxidase (Gl-Px), glutathione reductase (Gl-Red) and on the quantification of glutathione (GSH), glutathione-s-transferase (GST) and total antioxidant status (TAS). PC3 shows higher ROS production but also the highest GSH levels and Gl-Red activity, possibly contributing to oxidative stress resistance. This is also associated with higher mitochondrial membrane potential, TAS and lower lipid peroxidation. On the other hand, we identified Gl-Red activity reduction as a new strategy in overcoming oxidative stress resistance, by inducing H2O2 cytotoxicity. Therefore these results suggest Gl-Red activity reduction as a new potential therapeutic approach, in prostate cancer.
DOI: 10.1016/j.fob.2012.05.001
Rights: openAccess
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais

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