Abstract
It is a known paradox that many TGF beta 1-producing tumor cells are resistant to this, otherwise, inhibitory cytokine. In a lymphoma of B-cell origin exogenous TGF beta 1 was able to induce apoptosis, suggesting that the apoptosis program can be switched on. The apoptosis induction was independent of the death receptors but dependent on mitochondrial pathway and caspase-3. Probably due to the weak starting signal, caspase-3 further activated caspase-8 which, through the Bid cleavage and Bax translocation into the mitochondria, provided an autocatalytic support for the apoptotic program. There is a time-gat between the early activation of Smad-dependent TIEG and the accumulation of ROS, therefore other participants that start the increase in mitochondrial membrane permeability should be identified.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects
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Apoptosis / physiology*
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Caspase 8
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Caspase 9
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Caspases / metabolism*
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DNA-Binding Proteins / physiology
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Early Growth Response Transcription Factors
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Enzyme Activation / drug effects
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Humans
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Intracellular Membranes / drug effects
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Intracellular Membranes / physiology
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Kruppel-Like Transcription Factors
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Lymphoma, B-Cell / drug therapy
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Lymphoma, B-Cell / enzymology
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Lymphoma, B-Cell / pathology*
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Membrane Potentials / drug effects
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Membrane Potentials / physiology
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Mitochondria / drug effects
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Mitochondria / physiology*
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Reactive Oxygen Species / metabolism
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Transcription Factors / physiology
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Transforming Growth Factor beta / pharmacology*
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Transforming Growth Factor beta1
Substances
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DNA-Binding Proteins
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Early Growth Response Transcription Factors
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KLF10 protein, human
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Kruppel-Like Transcription Factors
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Reactive Oxygen Species
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TGFB1 protein, human
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Transcription Factors
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Transforming Growth Factor beta
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Transforming Growth Factor beta1
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CASP8 protein, human
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CASP9 protein, human
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Caspase 8
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Caspase 9
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Caspases