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Traffic. 2017 Aug;18(8):530-544. doi: 10.1111/tra.12493. Epub 2017 Jun 30.

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

Author information

1
Metabolism and Signaling in Cancer, BioMed X Innovation Center, Heidelberg, Germany.
2
Medicinal Chemistry, Merck Biopharma, Merck KGaA, Darmstadt, Germany.
3
Translational Innovation Platform Oncology, Merck Biopharma, Merck KGaA, Darmstadt, Germany.

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 (BFA), 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, BFA has not passed the preclinical stage of drug development. Recently, AMF-26 and golgicide A have been described as novel inhibitors of the Golgi system with antitumor or bactericidal properties. We provide here further evidence that AMF-26 closely mirrors the mode of action of BFA but is less potent. Using several human cancer cell lines, we studied the effects of AMF-26, BFA and golgicide A on cell homeostasis including Golgi structure, endoplasmic reticulum (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.

KEYWORDS:

AMF-26 ; ARF GTPase ; Golgi fragmentation; Golgi stress; brefeldin A; golgicide A

PMID:
28485883
DOI:
10.1111/tra.12493
[Indexed for MEDLINE]
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