학술논문
Inhibition of transforming growth factor beta1-induced hepatoma cell apoptosis by liver tumor promoters: characterization of primary signaling events and effects on CPP32-like caspase activity.
Document Type
Article
Author
Source
Subject
*CELL death
*HEPATOCELLULAR carcinoma
*TRANSFORMING growth factors-beta
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Language
ISSN
1350-9047
Abstract
The effects of the liver tumor promoters phenobarbital, clofibrate, dieldrin, and DDT on transforming growth factor-β1 (TGFβ)-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 apoptosis-associated cellular signaling proteins were observed: insulin led to an activation of the MAP kinases ERK1/2, of PKB/Akt and of NF-κB, phenobarbital and clofibrate enhanced NF-κB activity solely, while dexamethasone slightly enhanced NF-κB activity and increased the expression of Bcl-X[sub L]. Since inhibition of apoptosis was still detectable if the anti-apoptotic compounds were administered more than 10 h after TGFβ, the diverse primary signals appear to converge at a presumably late stage of apoptosis, but upstream of activation of CPP32 or related caspases. [ABSTRACT FROM AUTHOR]