This study characterises the expression of IAP in three of the most commonly used prostate cancer cells. IAP may make an important contribution to apoptotic resistance in patients with prostate cancer.

Resolution of neutrophil mediated inflammation is achieved, in part, through induction of neutrophil apoptosis. This constitutively expressed programme can be delayed by inflammatory mediators and induced by ligation of the Fas receptor. However, functional activation of the neutrophil results in resistance to Fas signalled death. We evaluated the effects of Fas antibody engagement on caspase activation and mitochondrial permeability, and the impact of co-stimulation by lipopolysaccharide (LPS) or granulocyte macrophage-colony stimulating factor (GM-CSF) on these events. Fas engagement by an agonistic anti-Fas antibody resulted in enhanced caspase 3 and 8 activity and increased mitochondrial permeability. Studies with pharmacological inhibitors of caspase activity showed that activation of caspase 8 occurred before, and activation of caspase 3 occurred after mitochondrial disruption. The mitochondrial stabilising agent bongkrekic acid also inhibited caspase activation and apoptosis. LPS, GM-CSF and increased glutathione stabilised the mitochondria and inhibited caspase 3. Caspase 8 activity was also inhibited by co-stimulation through a mechanism independent of mitochondrial stabilisation. Glutathione directly inhibited caspase 3 and 8 activity. We conclude inhibition of Fas antibody induced apoptosis by inflammatory proteins is associated with augmented mitochondrial stability and reduced caspase 3 activity that may be glutathione mediated.z 1999 Federation of European Biochemical Societies.

BACKGROUND Resistance to apoptosis remains a significant problem in the treatment of prostate cancer. Heat‐shock proteins (HSP) have been correlated with tumor progression. The role of HSP in prostate cancer resistance to apoptosis is unknown. METHODS PC‐3 and LNCaP prostate cancer cells were heat‐shocked and then treated with or without diethyl‐maleate, etoposide, cycloheximide, or 3 Gray irradiation. Percent apoptosis was assessed by propidium iodide DNA incorporation. Protein was also extracted for analysis by SDS‐PAGE Western blotting. RESULTS Western blotting confirmed an increase in HSP 27 and 72. These cells were resistant to both chemical‐ and radiation‐induced apoptosis. Cycloheximide and specific oligonucleotides to HSP 72 blocked the increased expression of HSP 72 and the resistance to apoptosis. Mcl‐1, Bcl‐2, Bcl‐XL, and glutathione‐S‐transferase (GST) expression were increased in a time‐dependent manner after heat shocke. CONCLUSIONS This study demonstrates that HSP expression, specifically HSP 72, inhibits apoptosis in prostate tumor cell lines, which may be mediated by the production of survival factors. Prostate 45:58–65, 2000. © 2000 Wiley‐Liss, Inc.