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. 2010 Sep 28;103(9):1380–1390. doi: 10.1038/sj.bjc.6605896

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Copyright © 2010 Cancer Research UK

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Combined treatment of fenretinide, etoposide or actinomycin D with TRAIL results in enhanced cell death. Treatment of ESFT cells with fenretinide leads to mitochondrial-dependent apoptosis through ROS generation, and ASK1-induced phosphorylation of p38^MAPK. Fenretinide treatment also results in ASK1- and p38α-mediated upregulation of DR at the cell surface. Etoposide and actinomycin D had similar effects. Treatment with ligands to the cognate DR resulted in enhanced cell death, which was mediated through both caspase-8 and Bid cleavage (tBid=truncated Bid).