S-1-O-phosphocholine-2-N-acetyl-octadecane induces apoptosis in T cells: Involvement of receptor activation and the intrinsic apoptotic pathway

Alkylphosphocholines (APC) represent compounds with far-ranging biological activities including inhibition of neoplastic cell growth in vivo and in vitro. Here we introduce the apoptosis-inducing activity of a newly synthesised APC, the S-NC-2, in Jurkat T cells. The results point to a dual apoptotic mechanism, a death receptor dependent activation as well as a death receptor-independent and mitochondria related pathway. The participation of the CD95 death receptor was determined by immunohistochemistry. Receptor aggregation and capping was already induced after 2 h of treatment with S-NC-2. We further analysed phosphatidylserin externalisation, chromatin condensation, the cleavage of procaspases-8, -9 and -3 and the degradation of caspase substrates. Comparison of Jurkat wildtype with FADD- and caspase-8-deficient cells and, additionally, the Bcl-2 overexpressing variant revealed a more detailed model of the APC-induced apoptosis. The lack of FADD or caspase-8 resulted in a somehow decreased amount of apoptotic cells, whereas the overexpression of Bcl-2 leads to a complete reduction of apoptosis and caspase-activation. After stimulation of death receptors such as CD95, the amplification via intrinsic apoptotic pathways is strongly required in Type II T cells.