The search for treatment options promoting TRAIL-mediated tumor cell killing is therefore as intense as ever.
However, it seems likely that continuous low-level IFN production during the chronic stage of infection is likely to be detrimental to the host and contribute to disease, for example by promoting TRAIL-mediated bystander apoptosis of CD4 T cells (Barblu et al., 2012; Hardy et al., 2007; Stary et al., 2009).
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It was suggested that hypermethylation of DR4 CpG island can promote TRAIL radioresistance [ 98].
The downregulation of Akt activity by LY294002 promoted TRAIL cytotoxicity in LO2 cells, implying that low oxidative stress induced by FeSOD inhibited TRAIL-induced apoptosis in the LO2 cells.
Based on these reports, it is possible that HGF might dissociate c-Met from TRAIL receptors and thereby promote TRAIL-induced cell death [ 19].
As such, both agents demonstrate the ability to promote TRAIL-mediated caspase-8 activation, suggesting that they likely act on upstream molecules of the pathway.
Biochemical analysis confirmed that while macrophages inhibited TRAIL-induced activation of caspase 8 and caspase-9 and cleavage of PARP and β-catenin, treatment with vitamin D3 promoted TRAIL-mediated activation of the apoptotic cascade in tumor cells that were grown in the presence of WT, but not VDR deficient macrophages (Fig. 4B).
We show that HGF promotes TRAIL-induced cell death in the human medulloblastoma DAOY cell line.
We found that in a representative medulloblastoma cell line, HGF promotes TRAIL-induced medulloblastoma cell death.
