Sulindac sulfide induces autophagic death in gastric epithelial cells via Survivin down-regulation: A mechanism of NSAIDs-induced gastric injury

Caloric restriction reveals a metabolomic and lipidomic signature in liver of male mice

“…This process requires cleavage of LC3 by Atg 4 to form cytosolic LC3-I. Subsequently, LC3-I undergoes conjugation to PE moiety by the Atg 7 and Atg 3 enzymes, to finally generate LC3-II, which is incorporated into the autophagosome membrane by the Atg 12-Atg 5-Atg 16 complex (Chiou et al ., 2011). It has been shown that Atg 7 protein levels increased in skeletal muscle of 24-month-old rats under 8% CR but LC3-I and LC3-II levels were unaffected (Wohlgemuth et al ., 2010).…”

Development of GI-safe NSAID; progression from the bark of willow tree to modern pharmacology

“…Excessive autophagy induction could lead to a non-apoptotic cell death, autophagic cell death. Sulindac sulfide at a physiological concentration also induces autophagic death in both human gastric epithelial AGS and rat gastric epithelial RGM-1 cells because increased LC3b-II and APG7 levels and cytosolic vacuole formation was observed after sulindac, indicating autophagy induction after NSAIDs [37]. Since cell death with sulindac was significantly reduced by pretreatment with the autophagy inhibitors 3-methyladenine and chloroquine, and downregulation of survivin was noted in the autophagy pathway downstream of LC3b-II induction by sulindac sulfide, NSAID cytotoxicity is associated with autophagy.…”

“…Therefore, autophagy inhibition can tackle the progression of NSAID cytotoxic mechanisms. Either pharmacological inhibition of autophagy with chloroquine or genetic ablation of LC3B autophagic gene can be anticipating strategy to secure GI safety [37].…”

Oxidative stress and inflammation in cerebral cavernous malformation disease pathogenesis: Two sides of the same coin

“…Indeed, it is well established that autophagy inducers limit ROS accumulation and oxidative stress by stimulating the autophagic degradation of ROS-generating mitochondria (Lee et al, 2012, Scherz-Shouval and Elazar, 2011). On the other hand, there is compelling evidence that antioxidant compounds, such as those indicated above, can induce autophagy, including statins (Andres et al, 2014, Wei et al, 2013, Zhang et al, 2013a), fasudil (Iorio et al, 2010), sulindac derivatives (Chiou et al, 2011, Gurpinar et al, 2013), and vitamin D3 (Hoyer-Hansen et al, 2010, Kim et al, 2012, Lisse and Hewison, 2011, Wu and Sun, 2011). Together with recent findings suggesting that the interplay between defective autophagy and redox imbalance may be integral to the development and progression of CCM lesions by sensitizing endothelial cells to local oxidative stress events (Marchi et al, 2015), these observations point to autophagy as a major redox-sensitive mechanism that justifies the reported effectiveness of the different potential therapeutic compounds described so far (Marchi et al, 2016a, Marchi et al, 2016b).…”