Cell survival and protein secretion associated with Golgi integrity in response to Golgi stress ‐inducing agents

Abstract The Golgi apparatus is part of the secretory pathway and of central importance for modification, transport and sorting of proteins and lipids. ADP‐ribosylation factors, whose activation can be blocked by brefeldin A, play a major role in functioning of the Golgi network and regulation of membrane traffic and are also involved in proliferation and migration of cancer cells. Due to high cytotoxicity and poor bioavailability brefeldin A has not passed the pre‐clinical stage of drug development. Recently, AMF‐26 and golgicide A have been described as novel inhibitors of the Golgi system with anti‐tumor or bactericidal properties. We provide here further evidence that AMF‐26 closely mirrors the mode of action of brefeldin A but is less potent. Using several human cancer cell lines, we studied the effects of AMF‐26, brefeldin A and golgicide A on cell homeostasis including Golgi structure, ER stress markers, secretion and viability, and found overall a significant correlation between these parameters. Furthermore, modulation of ADP‐ribosylation factor expression has a profound impact on Golgi organization and survival in response to Golgi stress inducers. Synopsis statement The small molecules AMF‐26, brefeldin A (BFA) and golgicide A (GCA) are inhibitors of protein trafficking and cause Golgi complex disintegration. We show here that AMF‐26 has a comparable mechanism of action to BFA but is less potent. Modulation of ARF GTPase isoform levels, in partic...
Source: Traffic - Category: Research Authors: Tags: ORIGINAL ARTICLE Source Type: research