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Smac mimetic bypasses apoptosis resistance in FADD- or caspase-8-deficient cells by priming for tumor necrosis factor α-induced necroptosis

(2011) NEOPLASIA. 13(10). p.971-U125
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Abstract
Searching for new strategies to bypass apoptosis resistance, we investigated the potential of the Smac mimetic BV6 in Jurkat leukemia cells deficient in key molecules of the death receptor pathway. Here, we demonstrate for the first time that Smac mimetic primes apoptosis-resistant, FADD-or caspase-8-deficient leukemia cells for TNF alpha-induced necroptosis in a synergistic manner. In contrast to TNF alpha, Smac mimetic significantly enhances CD95-induced apoptosis in wild-type but not in FADD-deficient cells. Interestingly, Smacmimetic- and TNF alpha-mediated cell death occurs without characteristic features of apoptosis (i.e., caspase activation, DNA fragmentation) in FADD-deficient cells. By comparison, Smac mimetic and TNF alpha trigger activation of caspase-8, -9, and -3 and DNA fragmentation in wild-type cells. Consistently, the caspase inhibitor zVAD. fmk fails to block Smac mimetic-and TNF alpha-triggered cell death in FADD-or caspase-8-deficient cells, while it confers protection in wild-type cells. By comparison, necrostatin-1, an RIP1 kinase inhibitor, abolishes Smac mimetic-and TNFa-induced cell death in FADD-or caspase-8-deficient. Thus, Smac mimetic enhances TNFa-induced cell death in leukemia cells via two distinct pathways in a context-dependent manner: it primes apoptosis-resistant cells lacking FADD or caspase-8 to TNF alpha-induced, RIP1-dependent and caspase-independent necroptosis, whereas it sensitizes apoptosis-proficient cells to TNF alpha-mediated, caspase-dependent apoptosis. These findings have important implications for the therapeutic exploitation of necroptosis as an alternative cell death program to overcome apoptosis resistance.
Keywords
DEATH, IN-VITRO, RIP1 KINASE, DEPENDENT APOPTOSIS, KAPPA-B ACTIVATION, CANCER, FAS, MOLECULE, RECEPTOR, CIAP1

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MLA
Laukens, Bram, et al. “Smac Mimetic Bypasses Apoptosis Resistance in FADD- or Caspase-8-Deficient Cells by Priming for Tumor Necrosis Factor α-Induced Necroptosis.” NEOPLASIA, vol. 13, no. 10, 2011, pp. 971-U125, doi:10.1593/neo.11610.
APA
Laukens, B., Jennewein, C., Schenk, B., Vanlangenakker, N., Schier, A., Cristofanon, S., … Fulda, S. (2011). Smac mimetic bypasses apoptosis resistance in FADD- or caspase-8-deficient cells by priming for tumor necrosis factor α-induced necroptosis. NEOPLASIA, 13(10), 971-U125. https://doi.org/10.1593/neo.11610
Chicago author-date
Laukens, Bram, Claudia Jennewein, Barbara Schenk, Nele Vanlangenakker, Alexander Schier, Silvia Cristofanon, Kerry Zobel, et al. 2011. “Smac Mimetic Bypasses Apoptosis Resistance in FADD- or Caspase-8-Deficient Cells by Priming for Tumor Necrosis Factor α-Induced Necroptosis.” NEOPLASIA 13 (10): 971-U125. https://doi.org/10.1593/neo.11610.
Chicago author-date (all authors)
Laukens, Bram, Claudia Jennewein, Barbara Schenk, Nele Vanlangenakker, Alexander Schier, Silvia Cristofanon, Kerry Zobel, Kurt Deshayes, Domagoj Vucic, Irmela Jeremias, Mathieu Bertrand, Peter Vandenabeele, and Simone Fulda. 2011. “Smac Mimetic Bypasses Apoptosis Resistance in FADD- or Caspase-8-Deficient Cells by Priming for Tumor Necrosis Factor α-Induced Necroptosis.” NEOPLASIA 13 (10): 971-U125. doi:10.1593/neo.11610.
Vancouver
1.
Laukens B, Jennewein C, Schenk B, Vanlangenakker N, Schier A, Cristofanon S, et al. Smac mimetic bypasses apoptosis resistance in FADD- or caspase-8-deficient cells by priming for tumor necrosis factor α-induced necroptosis. NEOPLASIA. 2011;13(10):971-U125.
IEEE
[1]
B. Laukens et al., “Smac mimetic bypasses apoptosis resistance in FADD- or caspase-8-deficient cells by priming for tumor necrosis factor α-induced necroptosis,” NEOPLASIA, vol. 13, no. 10, pp. 971-U125, 2011.
@article{1996538,
  abstract     = {{Searching for new strategies to bypass apoptosis resistance, we investigated the potential of the Smac mimetic BV6 in Jurkat leukemia cells deficient in key molecules of the death receptor pathway. Here, we demonstrate for the first time that Smac mimetic primes apoptosis-resistant, FADD-or caspase-8-deficient leukemia cells for TNF alpha-induced necroptosis in a synergistic manner. In contrast to TNF alpha, Smac mimetic significantly enhances CD95-induced apoptosis in wild-type but not in FADD-deficient cells. Interestingly, Smacmimetic- and TNF alpha-mediated cell death occurs without characteristic features of apoptosis (i.e., caspase activation, DNA fragmentation) in FADD-deficient cells. By comparison, Smac mimetic and TNF alpha trigger activation of caspase-8, -9, and -3 and DNA fragmentation in wild-type cells. Consistently, the caspase inhibitor zVAD. fmk fails to block Smac mimetic-and TNF alpha-triggered cell death in FADD-or caspase-8-deficient cells, while it confers protection in wild-type cells. By comparison, necrostatin-1, an RIP1 kinase inhibitor, abolishes Smac mimetic-and TNFa-induced cell death in FADD-or caspase-8-deficient. Thus, Smac mimetic enhances TNFa-induced cell death in leukemia cells via two distinct pathways in a context-dependent manner: it primes apoptosis-resistant cells lacking FADD or caspase-8 to TNF alpha-induced, RIP1-dependent and caspase-independent necroptosis, whereas it sensitizes apoptosis-proficient cells to TNF alpha-mediated, caspase-dependent apoptosis. These findings have important implications for the therapeutic exploitation of necroptosis as an alternative cell death program to overcome apoptosis resistance.}},
  author       = {{Laukens, Bram and Jennewein, Claudia and Schenk, Barbara and Vanlangenakker, Nele and Schier, Alexander and Cristofanon, Silvia and Zobel, Kerry and Deshayes, Kurt and Vucic, Domagoj and Jeremias, Irmela and Bertrand, Mathieu and Vandenabeele, Peter and Fulda, Simone}},
  issn         = {{1522-8002}},
  journal      = {{NEOPLASIA}},
  keywords     = {{DEATH,IN-VITRO,RIP1 KINASE,DEPENDENT APOPTOSIS,KAPPA-B ACTIVATION,CANCER,FAS,MOLECULE,RECEPTOR,CIAP1}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{971--U125}},
  title        = {{Smac mimetic bypasses apoptosis resistance in FADD- or caspase-8-deficient cells by priming for tumor necrosis factor α-induced necroptosis}},
  url          = {{http://dx.doi.org/10.1593/neo.11610}},
  volume       = {{13}},
  year         = {{2011}},
}

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