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Apoptosis. 2009 May;14(5):687-98. doi: 10.1007/s10495-009-0337-7.

The involvement of mitochondria and the caspase-9 activation pathway in rituximab-induced apoptosis in FL cells.

Author information

1
Department of Clinical Microbiology, University of Kuopio, Yliopistoranta 1C, 70210, Kuopio, Finland. eeva@hytti.uku.fi

Abstract

Despite the wide use of anti-CD20 antibody rituximab in the cancer treatment of B cell malignancies, the signalling pathways of CD20-induced apoptosis are still not understood. By using dominant negative (DN)-caspase-9 overexpressing follicular lymphoma cells we demonstrated that the activation of caspase-9 was essential for rituximab-mediated apoptosis. The death receptor pathway mediated by caspase-8 activation was not involved in rituximab-mediated apoptosis since overexpression of FLIP(short) or FLIP(long) proteins, inhibitors of caspase-8 activation, could not inhibit rituximab-induced apoptosis. However, the death receptor pathway activation by anti-Fas antibodies showed an additive effect on rituximab-induced apoptosis. The stabilisation of the mitochondrial outer membrane by Bcl-x(L) overexpression inhibited cell death, showing the important role of mitochondria in rituximab-induced apoptosis. Interestingly, the rituximab-induced release of cytochrome c and collapse of mitochondrial membrane potential were regulated by caspase-9. We suggest that caspase-9 and downstream caspases may feed back to mitochondria to amplify mitochondrial disruption during intrinsic apoptosis.

PMID:
19308735
DOI:
10.1007/s10495-009-0337-7
[Indexed for MEDLINE]

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