National Cancer Institute®
Last Modified: June 1, 2002
UI - 11894131
AU - Mori S; Murakami-Mori K; Nakamura S; Bonavida B
TI - Actinomycin D-mediated sensitization of AIDS-Kaposi's sarcoma cells to Fas-mediated apoptosis: involvement of the mitochondrion-dependent pathway.
SO - Int J Oncol 2002 Apr;20(4):819-26
AD - Department of Microbiology, Immunology, and Molecular Genetics, UCLA School of Medicine, University of California, Los Angeles, CA 90095, USA.
Fas engagement rapidly induces formation of the death-inducing signaling complex (DISC) that consists of Fas, FADD and pro-caspase-8. Activated caspase-8 at the DISC directly activates downstream caspases, resulting in induction of apoptosis of the independent mitochondria. In this study, we have obtained evidence demonstrating that Fas-mediated apoptosis in AIDS-KS cells takes place in a mitochondria-dependent manner. FADD and pro-caspase-8 were detected in immunoprecipitates with anti-Fas antibody in anti-Fas mAb (CH-11)-treated Hut 78, a typical Fas-sensitive cell line. On the other hand, DISC formation by CH-11 was markedly reduced in AIDS-KS cells. In addition, CH-11-induced activation of caspase-8-like protease in AIDS-KS cells was much less pronounced compared with that in Hut 78; however, a caspase-8 inhibitor, zIETD-fmk, completely blocked the apoptosis. Further, a caspase-9 inhibitor, zLEHD-fmk, markedly inhibited Fas-mediated apoptosis in AIDS-KS cells. Several apoptotic stimuli induce mitochondria activation allowing cytochrome c release from the mitochondria. In the apoptosome, cytochrome c and Apaf-1 activate caspase-9 which subsequently leads to the activation of caspase-3. In AIDS-KS cells, CH-11 triggered cytochrome c release, an event which was inhibited by zIETD-fmk. Further, a caspase-3 inhibitor, zDEVD-fmk completely inhibited the apoptosis. Altogether, the present data provide evidence that the Fas signal in AIDS-KS cells is preferentially transduced through the mitochondria-dependent pathway, which is initiated by caspase-8 activation.
The above citations and abstracts reflect those newly added to CANCERLIT for the month and topic listed in the title. The citations have been retrieved from CANCERLIT using a predefined search strategy of indexed subject terms. Although the search strategy has been refined as best as possible, citations may appear that are not directly related to the topic, and occasionally relevant references may be omitted.