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|Title:||The role of reactive oxygen species and autophagy in safingol-induced cell death|
Glucose uptake inhibition
|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. https://doi.org/10.1038/cddis.2011.12|
|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|
|Appears in Collections:||Staff Publications|
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