Subtype-selective inhibition of acid-sensing ion channel 3 by a natural flavonoid.

Aims: Acid-sensing ion channels (ASICs) are extracellular proton-gated cation channels that have been implicated in multiple physiological and pathological processes, and peripheral ASIC3 prominently participate into the pathogenesis of chronic pain, itch, and neuroinflammation, which necessitates the need for discovery and development of novel modulators in a subtype-specific manner.

Methods: Whole-cell patch clamp recordings and behavioral assays were used to examine the effect of several natural compounds on the ASIC-mediated currents and acid-induced nocifensive behavior, respectively.

Results: We identified a natural flavonoid compound, (-)-epigallocatechin gallate (EGCG, compound 11), that acts as a potent inhibitor for the ASIC3 channel in an isoform-specific way.

Alisertib induces cell cycle arrest and autophagy and suppresses epithelial-to-mesenchymal transition involving PI3K/Akt/mTOR and sirtuin 1-mediated signaling pathways in human pancreatic cancer cells.

Pancreatic cancer is the most aggressive cancer worldwide with poor response to current therapeutics. Alisertib (ALS), a potent and selective Aurora kinase A inhibitor, exhibits potent anticancer effects in preclinical and clinical studies; however, the effect and underlying mechanism of ALS in the pancreatic cancer treatment remain elusive. This study aimed to examine the effects of ALS on cell growth, autophagy, and epithelial-to-mesenchymal transition (EMT) and to delineate the possible molecular mechanisms in human pancreatic cancer PANC-1 and BxPC-3 cells.