Fenretinide-dependent upregulation of death receptors through ASK1 and p38α enhances death receptor ligand-induced cell death in Ewing's sarcoma family of tumours.

ABSTRACT:

Background

Sustained p38(MAPK) phosphorylation upregulates p75 neurotrophin (p75(NTR)) and induces apoptosis in Ewing's sarcoma family of tumours (ESFT). As fenretinide induces ESFT death through sustained p38(MAPK) phosphorylation, we hypothesised that this may be effected through upregulation of death receptors (DRs) and that treatment of fenretinide plus DR ligands may enhance apoptosis.

Methods

DR expression was determined by flow cytometry. Trypan blue exclusion assays, caspase-8 flow cytometry and immunoblotting for Bid were used to measure cell death.

Results

Fenretinide upregulated cell surface expression of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors, FAS and p75(NTR), in an ASK1- and p38α-dependent manner. Cotreatment with fenr

SUBMITTER: White DE 

PROVIDER: S-EPMC2990598 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature