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The Alkyllysophospholipid Edelfosine Enhances TRAIL-mediated Apoptosis in Gastric Cancer Cells Through Death Receptor 5 and the Mitochondrial Pathway

Sung-Chul Lim, Keshab Raj Parajuli, Song Iy Han

Tumour Biol. 2016 May;37(5):6205-16.

PMID: 26615420

Abstract:

The ether phospholipid edelfosine is the prototype of a group of synthetic antitumor alkyllysophospholipid (ALP) compounds that exert pro-apoptotic effects in various types of cancer cells through cell type-dependent mechanisms. In this study, we examined the antitumor effect of edelfosine in human gastric cancer cells. Edelfosine decreased cell viability and induced autophagic death at a moderate concentration (~30 μM), whereas it induced apoptotic cell death at concentrations over 30 μM. Interestingly, low concentrations of edelfosine (5-10 μM) effectively enhanced recombinant human tumor necrosis factor (TNF)-related apoptosis-inducing ligand (rhTRAIL/TNFSF10)-induced apoptosis and clonogenicity in gastric cancer cells, including TRAIL-resistant AGS cells. Edelfosine upregulated the protein level of death receptor 5 (DR5/TNFRSF10B) and/or increased DR5 upregulation in lipid rafts. In addition, edelfosine-mediated rhTRAIL sensitization was regulated by the DR5 pathway. Edelfosine also activated p38MAPK (MAPK14), and edelfosine-mediated rhTRAIL sensitization was partially regulated by a p38-mediated decrease in mitochondrial membrane potential. This study suggests a novel therapeutic strategy targeting gastric cancer cells by using the combination of edelfosine and TRAIL.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP70641519-A Edelfosine Edelfosine 70641-51-9 Price
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