Actinomycin D-mediated sensitization of AIDS-Kaposi's sarcoma cells to Fas-mediated apoptosis: Involvement of the mitochondrion-dependent pathway

  • Authors:
    • Shunsuke Mori
    • Kaoru Murakami-Mori
    • Shuji Nakamura
    • Benjamin Bonavida
  • View Affiliations

  • Published online on: April 1, 2002     https://doi.org/10.3892/ijo.20.4.819
  • Pages: 819-826
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Abstract

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.

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April 2002
Volume 20 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Mori S, Murakami-Mori K, Nakamura S and Bonavida B: Actinomycin D-mediated sensitization of AIDS-Kaposi's sarcoma cells to Fas-mediated apoptosis: Involvement of the mitochondrion-dependent pathway. Int J Oncol 20: 819-826, 2002
APA
Mori, S., Murakami-Mori, K., Nakamura, S., & Bonavida, B. (2002). Actinomycin D-mediated sensitization of AIDS-Kaposi's sarcoma cells to Fas-mediated apoptosis: Involvement of the mitochondrion-dependent pathway. International Journal of Oncology, 20, 819-826. https://doi.org/10.3892/ijo.20.4.819
MLA
Mori, S., Murakami-Mori, K., Nakamura, S., Bonavida, B."Actinomycin D-mediated sensitization of AIDS-Kaposi's sarcoma cells to Fas-mediated apoptosis: Involvement of the mitochondrion-dependent pathway". International Journal of Oncology 20.4 (2002): 819-826.
Chicago
Mori, S., Murakami-Mori, K., Nakamura, S., Bonavida, B."Actinomycin D-mediated sensitization of AIDS-Kaposi's sarcoma cells to Fas-mediated apoptosis: Involvement of the mitochondrion-dependent pathway". International Journal of Oncology 20, no. 4 (2002): 819-826. https://doi.org/10.3892/ijo.20.4.819