DNA damage- induced apoptosis in the BL30A Burkitt’s lymphoma cell line requires caspase-8 and mitochondrial p53 activity.

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Wilkie, Alexander
Leung, Donmienne
Finney, Lauren
Fairlie, David
Watters, Dianne Josephine
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2011
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ClubMed Lindeman Island, Queensland

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Abstract

Caspase-8, the apical caspase in the extrinsic apoptotic signalling pathway is normally activated by binding of a death ligand to death receptor. Caspase-9 is considered to be the apical caspase in the intrinsic apoptotic pathway and is usually activated by stimuli such as DNA damage. In the BL30A Burkitt’s lymphoma cell line, caspase-8 appears to be the apical caspase following DNA damage as evidenced by the use of selective caspase inhibitors, and trapping using the pan-caspase inhibitor biotinylated VAD-fmk. These cells do not undergo apoptosis in response to Fas ligation and contain internal Fas as has been reported for similar Burkitt’s lymphoma cell lines. These cells are also reported to have one mutant allele of p53 and one deleted allele. We have explored the apoptotic pathway in response to DNA damage (etoposide) in BL30A cells by examining the time course of activation of caspase-8 and cytochrome C release, both of which occur between 2 and 3 h post treatment. Selective inhibition of mitochondrial p53 activity by Pifithrin-µ effectively blocked apoptosis whereas inhibition of p53 transcriptional activity by Pifithrin-α failed to inhibit apoptosis. These results indicate that p53 mitochondrial activity and caspase-8 activation are required for apoptosis to proceed in BL30A cells following etoposide treatment.

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Proceedings of the 1st Australian Workshop on Cell Death, 2011

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Cell Development, Proliferation and Death

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