Oxidative stress and glyoxalase I activity mediate dicarbonyl toxicity in MCF-7 mamma carcinoma cells and a tamoxifen resistant derivative.

摘要: Abstract Background Acquired tamoxifen resistance is a significant problem in estrogen receptor positive breast cancer. In cellular model, was associated with increased sensitivity towards toxic dicarbonyls and reduced free sulfhydryl group content. We here analyzed the role of oxidative stress glyoxalase I activity on dicarbonyl significance expression for survival. Methods Reactive oxygen species were determined by 2,7-dihydrochlorofluorescein diacetate. Inhibitors NADPH-oxidase (diphenyleneiodonium), p38 MAPK (SB203580) ERK1/2 (UO126) applied to investigate interactions these signaling molecules. N-acetyl cysteine used evaluate effect cell viability, which assessed resazurin assay. Gene real time qRT-PCR. Glyoxalase inhibited specific inhibitor CS-0683 siRNA. The relevance 1 mRNA abundance survival cancer patients evaluated KM-plotter web interface. Results α-Oxo-aldehydes caused an immediate increase reactive where resistant line (TamR) responded at lower concentrations than MCF-7 parental line. Inhibitor studies placed ROS production downstream MAPK. antioxidant (NAC) survival, whereas (GLO1) inhibition toxicity. GLO1 correlated unfavorable prognosis patients. Conclusions Dicarbonyl toxicity mediated determines aldehyde cells. General Significance Glyoxalases might be predictive biomarkers putative target treatment