Scavenging of reactive oxygen species by astaxanthin inhibits epithelial–mesenchymal transition in high glucose-stimulated mesothelial cells

Abstract

BackgroundHigh glucose concentrations influence the functional and structural development of the peritoneal membrane. We previously reported that the oral administration of astaxanthin (AST) suppressed peritoneal fibrosis (PF) as well as inhibited oxidative stress, inflammation, and epithelial–mesenchymal transition (EMT) of peritoneal mesothelial cells (PMCs) in a chlorhexidine-induced PF rat model. This suggests that oxidative stress induction of EMT is a key event during peritoneal damage. The present study evaluated the therapeutic effect of AST in suppressing EMT, in response to glucose-induced oxidative stress.MethodsTemperature-sensitive mesothelial cells (TSMCs) were cultured in the presence or absence of AST and then treated with 140 mM glucose for 3 or 12 hours. Expression levels of TNF-α, TGF-β, and VEGF were determined at the mRNA and protein levels, and nuclear factor kappa B (NF-κB) activity was evaluated. We measured NO2−/NO3− concentrations in cellular supernatants and determined 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels in mitochondrial and nuclear DNA. The expressions of E-cadherin and alpha-smooth muscle actin (α-SMA) were evaluated by double immunofluorescence and protein levels.ResultsHigh glucose concentrations induced overproduction of reactive oxidative species (ROS), increasing 8-OHdG mitochondrial DNA and cytokine levels. The NF-κB pathway was activated in response to high glucose concentrations, whereas de novo α-SMA expression was observed with decreased E-cadherin expression. AST treatment attenuated ROS production, inflammatory cytokine production, NF-κB activation, and EMT.ConclusionThe findings of the present study indicate that AST may have an anti-EMT effect due to anti-oxidative and anti-inflammatory activities by scavenging glucose-induced ROS from mitochondria in PMCs. AST may be an efficacious treatment for PF.

Glycine and succinic acid are effective indicators of the suppression of epithelial-mesenchymal transition by fucoxanthinol in colorectal cancer stem-like cells

“…In the present study, we further showed that FxOH treatment began to suppress PPARγ and inhibit pC-Raf (Ser 338 ) starting at 4 h, and decreased amounts of vimentin or increased E-cadherin levels were observed at 8 h, followed by caspase-3 activation and p53 depression at 24 h in both Csps. A highly polar xanthophyll, astaxanthin, as well as FxOH both inhibit EMT accompanied by the attenuation of reactive oxygen species production, inflammatory cytokine production and NF-κB activation in rat peritoneal mesothelial cells (40). The apocarotenoids crocetin and crocin promote EMT attenuation by inhibiting N-cadherin and β-catenin expression and increasing E-cadherin expression in aggressive prostate cancer PC3 and 22rvl cells (41).…”

Mitochondrial Dysfunction Plays a Relevant Role in Pathophysiology of Peritoneal Membrane Damage Induced by Peritoneal Dialysis

“…In fact, the presence of free radicals in the effluent is associated with technique failure in stable PD patients [ 13 , 14 ]. Previous studies have demonstrated that glucose-rich and/or acidic hypertonic PD solutions could be associated with higher levels of oxidative stress [ 15 , 16 , 17 , 18 ]. The PD-related oxidative process can be modulated by drug treatments used in these patients [ 19 , 20 ].…”

Ferritinophagic Flux Activation in CT26 Cells Contributed to EMT Inhibition Induced by a Novel Iron Chelator, DpdtpA

“…Since redox regulates epithelial-mesenchymal transition of tumor cell, scavenging ROS favors restoration of MET (mesenchymal-to-epithelial transition), which may efficiently slow dissemination of tumor cells [18, 19]. A lot of compounds either from natural products or artificially synthesized exhibit the ability in EMT reversion; different signal pathway was proposed [20–23].…”