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: The proximal caspase in the Fas apoptotic pathway is Caspase 8. Recruitment and auto-cleavage of Procaspase 8 occurs following Fas receptor activation in sensitive cells. Active Caspase 8 is tetrameric, consisting of two P14 and two P10 subunits. Using Western blot analysis, we found that Caspase 8 is not cleaved in DU 145 cells following treatment with anti-Fas IgM (200 ng ml−1) (Figure 4AFigure 4
Affiliation: Department of Biochemistry, University College Cork, Lee Maltings, Prospect Row, Cork, Ireland.