TGF beta 1 kills lymphoma cells using mitochondrial apoptotic pathway with the help of caspase-8.
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.
Barna
Gabor
G
1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
Sebestyén
Anna
A
Chinopoulos
Christos C
CC
Nagy
Katalin
K
Mihalik
Rudolf
R
Paku
Sandor
S
Kopper
Laszlo
L
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000502:physiology; D051765:Early Growth Response Transcription Factors; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology; D051741:Kruppel-Like Transcription Factors; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014157:Transcription Factors / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1
D004268:DNA-Binding Proteins; D051765:Early Growth Response Transcription Factors; C098111:KLF10 protein, human; D051741:Kruppel-Like Transcription Factors; D017382:Reactive Oxygen Species; C508960:TGFB1 protein, human; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases