Please use this identifier to cite or link to this item:
Title: The role of reactive oxygen species and autophagy in safingol-induced cell death
Authors: Ling, L.-U.
Tan, K.-B.
Lin, H.
Chiu, G.N.C. 
Keywords: Autophagy
Glucose uptake inhibition
Issue Date: Mar-2011
Citation: Ling, L.-U., Tan, K.-B., Lin, H., Chiu, G.N.C. (2011-03). The role of reactive oxygen species and autophagy in safingol-induced cell death. Cell Death and Disease 2 (3) : -. ScholarBank@NUS Repository.
Abstract: Safingol is a sphingolipid with promising anticancer potential, which is currently in phase I clinical trial. Yet, the underlying mechanisms of its action remain largely unknown. We reported here that safingol-induced primarily accidental necrotic cell death in MDA-MB-231 and HT-29 cells, as shown by the increase in the percentage of cells stained positive for 7-aminoactinomycin D, collapse of mitochondria membrane potential and depletion of intracellular ATP. Importantly, safingol treatment produced time- and concentration-dependent reactive oxygen species (ROS) generation. Autophagy was triggered following safingol treatment, as reflected by the formation of autophagosomes, acidic vacuoles, increased light chain 3-II and Atg biomarkers expression. Interestingly, scavenging ROS with N-acetyl-L-cysteine could prevent the autophagic features and reverse safingol-induced necrosis. Our data also suggested that autophagy was a cell repair mechanism, as suppression of autophagy by 3-methyladenine or bafilomycin A1 significantly augmented cell death on 2-5 lM safingol treatment. In addition, Bcl-xL and Bax might be involved in the regulation of safingol-induced autophagy. Finally, glucose uptake was shown to be inhibited by safingol treatment, which was associated with an increase in p-AMPK expression. Taken together, our data suggested that ROS was the mediator of safingol-induced cancer cell death, and autophagy is likely to be a mechanism triggered to repair damages from ROS generation on safingol treatment. © 2011 Macmillan Publishers Limited All rights reserved.
Source Title: Cell Death and Disease
ISSN: 20414889
DOI: 10.1038/cddis.2011.12
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.


checked on Dec 13, 2018


checked on Dec 13, 2018

Page view(s)

checked on Sep 28, 2018

Google ScholarTM



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.