Anisomycin activates JNK and sensitises DU 145 prostate carcinoma cells to Fas mediated apoptosis.
Bottom Line: Our group has shown that inhibition of JNK activity completely abrogates the effects of chemotherapeutic drugs.Inhibition of Caspase 8 and Caspase 9 completely inhibits this process which suggests that DU 145 cells require mitochondrial amplification of the Fas apoptotic signal.Furthermore, we have shown that inhibition of Fas mediated apoptosis is an early event in DU 145 cells, occurring upstream of Caspase 8 cleavage.
Affiliation: Department of Biochemistry, University College Cork, Lee Maltings, Prospect Row, Cork, Ireland.Show MeSH
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Mentions: Various reports have shown that down-regulation of Fas receptor or Fas ligand expression occurs in some cancer cells. In addition, expression of Fas ligand has been reported to increase following JNK activation in Jurkat cells (Herr et al, 2000). This increase in Fas ligand expression caused an increase in the kinetics of Fas mediated apoptosis. We assessed the expression of both Fas receptor and Fas ligand over an 8 h period (1,2,4 and 8 h) following incubation with anisomycin (250 ng ml−1) or anti-Fas IgM (250 ng ml−1). Cell surface Fas receptor was expressed on 95% of DU 145 cells and its expression was not found to change following treatment with anisomycin or anti-Fas IgM (Figure 2AFigure 2
Affiliation: Department of Biochemistry, University College Cork, Lee Maltings, Prospect Row, Cork, Ireland.