Resistance to TRAIL-induced apoptosis in neuroblastoma cells correlates with a loss of caspase-8 expression

Eggert, Angelika; Grotzer, Michael A.; Zuzak, Tycho Jan; Wiewrodt, Barbara R.; Ikegaki, Naohiko; Brodeur, Garrett M.

doi:10.1002/1096-911x(20001201)35:6<603::aid-mpo24>3.0.co;2-1

Cited by 210 publications

(243 citation statements)

References 12 publications

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“…Resistance to Apo2L/TRAIL has been attributed to differential expression of death receptors, 33 defects in caspase-8, 34 higher expression of FLIP 9 or XIAP 19 or defects in Apaf-1 35 expression. Apo2L/TRAIL binds to its receptors, activates caspase-8 and results in cleavage of procaspase-3 to active caspase-3 (p20/p12), yet does not induce apoptosis in melanoma cells.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of Bcl-2, FLIP or IAPs (XIAP and survivin) by siRNAs sensitizes resistant melanoma cells to Apo2L/TRAIL-induced apoptosis

et al. 2004

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Melanoma cells are relatively resistant to Apo2L/TRAIL (TNFrelated apoptosis-inducing ligand). We postulated that resistance might result from higher expression of inhibitors of apoptosis including Bcl-2, FLIP (FLICE-like inhibitory protein) or IAPs such as XIAP (X-linked inhibitor of apoptosis) or survivin. Compared to scrambled or mismatch controls, targeting individual inhibitors with siRNA (si-Bcl-2, si-XIAP, si-FLIP or si-Surv), followed by Apo2L/TRAIL resulted in marked increase in apoptosis in melanoma cells. Compared to Bcl-2 or FLIP, siRNAs against XIAP and survivin were most potent in sensitizing melanoma cells. A similar substantial increase in apoptosis was seen in renal carcinoma cells (SKRC-45, Caki-2), following the inhibition of either XIAP or survivin by siRNAs. Apo2L/TRAIL treatment in IAP-targeted cells resulted in cleavage of Bid, activation of caspase-9 and cleavage of PARP (poly ADP-ribose polymerase). Thus, Apo2L/TRAIL resistance can be overcome by interfering with expression of inhibitors of apoptosis regulating both extrinsic (death receptor) or intrinsic (mitochondrial) pathways of apoptosis in melanoma cells.

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Section: Discussionmentioning

confidence: 99%

Downregulation of Bcl-2, FLIP or IAPs (XIAP and survivin) by siRNAs sensitizes resistant melanoma cells to Apo2L/TRAIL-induced apoptosis

et al. 2004

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“…The observed TRAIL induced activation of NF-κB and Akt could be important for tumor cells survival and proliferation [8,42,43]. The involvement of caspase 8 in apoptosis signaling is crucial in TRAIL induced apoptosis but its involvement in the proliferation signaling is overlapping with caspase 1 and thus loss of caspase 8 can block apoptosis but not proliferation [1][2][3][4]. Our data as well as previously reported [16,17] indicate that TRAIL-induced activation of caspases 1 and 8 is essential for up regulation of cytokines..…”

Section: Discussionmentioning

confidence: 99%

“…TRAIL resistance has been associated with several factors, including downregulation or loss of death receptors or caspase-8 [4], and overexpression of decoy receptors [5] or intracellular protein c-FLIP [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Multiple effects of TRAIL in human carcinoma cells: Induction of apoptosis, senescence, proliferation, and cytokine production

Levina

Marrangoni

DeMarco

et al. 2008

Experimental Cell Research

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TRAIL is a death ligand that induces apoptosis in malignant but not normal cells. Recently the ability of TRAIL to induce proliferation in apoptosis-resistant normal and malignant cells was reported. In this study, we analyzed TRAIL effects in apoptosis sensitive MCF7, OVCAR3 and H460 human tumor cell lines. TRAIL at low concentrations preferentially induced cell proliferation. At 100 ng/ ml apoptotic death was readily observed, however surviving cells acquired higher proliferative capacity. TRAIL stimulated production of several cytokines, IL-8, RANTES, MCP-1 and bFGF, and activation of caspases 1 and 8 was essential for this effect. Antibodies to IL-8, RANTES, and bFGF blocked TRAIL-induced cell proliferation and further stimulated apoptosis. For the first time, we report that high TRAIL concentrations induced cell senescence as determined by altered morphology and expression of several senescence markers: SA-β-gal, p21 Waf1/Cip1 , p16 INK4a , and HMGA. Caspase 9 inhibition protected TRAIL-treated cells from senescence, whereas inhibition of caspases 1 and 8 increased yield of SLP cells. In conclusion, in cultured human carcinoma cells, TRAIL therapy results in three functional outcomes, apoptosis, proliferation and senescence. TRAIL induced proapoptotic and prosurvival responses correlate with strength of signaling. TRAIL-induced cytokine production is responsible for its proliferative and prosurvival effects.

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“…Both recombinant, soluble TRAIL and wild-type, membrane-bound TRAIL induce apoptosis in a wide variety of transformed cell lines via interaction with one or both of the death receptors DR4/TRAIL-R1 and DR5/TRAIL-R2, 12,13 which in turn initiates activation of caspase-8 through FADD, leading to apoptosis. [14][15][16] However, the antagonistic decoy receptors DcR1, 17,18 DcR2, 19 and osteoprotegerin 20 are believed to protect normal cells from the cytotoxic effects of TRAIL by competing with DR4/TRAIL-R1 and DR5/TRAIL-R2 for TRAIL binding.…”

Section: In Either Dld1/bax-r or Dld1/trail-r Cells Bcl-xl Expressiomentioning

confidence: 99%

Mechanisms involved in development of resistance to adenovirus-mediated proapoptotic gene therapy in DLD1 human colon cancer cell line

Zhang

Lin

et al. 2002

Gene Ther

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Resistance to TRAIL-induced apoptosis in neuroblastoma cells correlates with a loss of caspase-8 expression

Cited by 210 publications

References 12 publications

Downregulation of Bcl-2, FLIP or IAPs (XIAP and survivin) by siRNAs sensitizes resistant melanoma cells to Apo2L/TRAIL-induced apoptosis

Downregulation of Bcl-2, FLIP or IAPs (XIAP and survivin) by siRNAs sensitizes resistant melanoma cells to Apo2L/TRAIL-induced apoptosis

Multiple effects of TRAIL in human carcinoma cells: Induction of apoptosis, senescence, proliferation, and cytokine production

Mechanisms involved in development of resistance to adenovirus-mediated proapoptotic gene therapy in DLD1 human colon cancer cell line

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