Cycloprodigiosin Hydrochloride Activates the Ras-PI3K-Akt Pathway and Suppresses Protein Synthesis Inhibition-Induced Apoptosis in PC12 Cells

摘要

Cycloprodigiosin hydrochloride(cPrG-HCl),a member of the prodigiosin family of compounds,has been reported to act as an H~+/CI~-symporter.This compound induces apoptosis in several cancer cells and acts as an antitumor drug in animal models.In this study,we found a novel function of cPrG-HCl;to suppress cell death in PC12 cells,which is caused by protein synthesis inhibitors cycloheximide and actinomycin D.cPrG-HCl activated Akt and suppressed apoptosis,and this was accompanied by inhibition of caspase-3 activity and DNA fragmentation independently of its H~+/Cl~-symporter activity.Wortmannin,a phosphatidylinositol 3-kinase(PI3K)inhibitor,and dominant-negative Ras attenuated the anti-apoptotic activity of cPrG-HCl,which indicates that cPrG-HCl activated the Ras-PI3K-Akt pathway suppressing apoptosis.On the other hand,serum-deprivation-induced apoptosis was not suppressed by cPrG-HCl.