Spautin-1

Spautin-1 is a specific and potent autophagy inhibitor-1. In Vitro: Spautin-1 enhances imatinib mesylate (IM)-induced CmL cell apoptosis by reducing the expression of the anti-apoptotic proteins Mcl-1 and Bcl-2. The pro-apoptotic activity of spautin-1 is associated with activation of GSK3β, an important downstream effector of PI3K/AKT. Spautin-1 enhances IM-induced cytotoxicity in CmL cell line K562, decreasing the IC₅₀ from 1 to 0.5 μM^[1]. The mechanism of spautin-1 acting on acute pancreatitis is associated with impaired autophagy inhibition^[2]. In Vivo: Spautin-1 ameliorates the pathogenesis of acute pancreatitis induced by cerulein or L-arginine. Spautin-1 pretreatment significantly diminishes the elevation of serum amylase and lipase levels, which are indicative of trypsin activity. Increasing levels of serum TNFα caused by cerulein are inhibited in the presence of spautin-1. Spautin-1 treatment can ameliorate the inflammation damage induced by cerulein, such as edema, degeneration, coagulative necrosis and infiltration of inflammatory cells^[2].