The effects of the liver tumor promoters phenobarbital, clofibrate, dieldrin, and DDT on transforming growth factor-b1 (TGFb)-induced apoptosis were studied in FTO-2B hepatoma cells. Inhibition of apoptosis by these compounds was strongly correlated with a decrease in CPP32-like caspase activity. Similar effects were obtained with insulin and dexamethasone. CPP32-like activity may thus provide a useful tool for quantiation of apoptosis under various treatment conditions. Diverse effects on

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... osis-associated cellular signaling proteins were observed: insulin led to an activation of the MAP kinases ERK1/2, of PKB/Akt and of NF-kB, phenobarbital and clofibrate enhanced NF-kB activity solely, while dexamethasone slightly enhanced NF-kB activity and increased the expression of Bcl-x L . Since inhibition of apoptosis was still detectable if the anti-apoptotic compounds were administered more than 10 h after TGFb, the diverse primary signals appear to converge at a presumably late stage of apoptosis, but upstream of activation of CPP32 or related caspases.