Induction of a TRAIL mediated suicide program by interferon alpha in primary effusion lymphoma

Toomey, Ngoc L.; Deyev, Vadim; Wood, Charles; Boise, Lawrence H.; Scott, D.E.; Liu, Lei Hua; Cabral, Lisa; Podack, Eckhard R.; Barber, Glen N.; Harrington, William J.

doi:10.1038/sj.onc.1204895

Cited by 62 publications

(55 citation statements)

References 43 publications

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“…Consistent with prior work, 17,18 TRAIL had minimal cytotoxic effects on its own with approximately 10% reduction in PEL cell viability at 48 h at a concentration up to 200 ng/ml (data not shown). Unlike the synergistic interactions between IFN-a and TRAIL, when we treated PELs with bortezomib and TRAIL in combination, median effect/CI analysis demonstrated additive interactions across all concentrations and all schedules of both bortezomib and TRAIL (Supplementary Figure 2).…”

Section: Drug Interactions Between Bortezomib and Trailsupporting

confidence: 91%

“…3,17,18 The pro-apoptotic effects of TRAIL, which ligates death receptors and thereby activates the extrinsic pathway of apoptosis, can be abrogated by its simultaneous activation of the antiapoptotic NF-kB pathway. 19,20 Thus, it was further demonstrated that AZT sensitized to TRAIL by blocking NF-kB activation.…”

Section: Drug Interactions Between Bortezomib and Trailmentioning

confidence: 99%

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Antitumor effects of bortezomib (PS-341) on primary effusion lymphomas

Sun

Fisher

et al. 2004

Leukemia

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Primary effusion lymphomas (PELs) are a rare type of nonHodgkin's lymphoma that are resistant to cytotoxic chemotherapy. PELs manifest constitutive activation of nuclear factor kappa B (NF-jB), and inhibition of NF-jB induces apoptosis of PELs and sensitizes to tumor necrosis factor-related apoptosisinducing ligand (TRAIL)-induced death. Bortezomib (PS-341), a peptidyl boronic acid inhibitor of the proteasome, is a potent agent against a wide range of hematologic malignancies and has been shown to inhibit NF-jB. Thus, we examined the cytotoxic effects of bortezomib alone and in combination with various drugs. Bortezomib potently inhibited NF-jB in PEL cells in a dose-dependent manner. In addition, bortezomib inhibited growth and induced apoptosis of PEL cell lines (IC 50 values of 3.4-5.0 nM). Results of drug interactions between bortezomib and chemotherapy (doxorubicin and Taxol) were scheduledependent: synergistic interactions were generally observed when PEL cells were pretreated with bortezomib prior to chemotherapy, whereas additive or even antagonistic interactions occurred with chemotherapy pretreatment or simultaneous treatment with bortezomib and chemotherapy. Most schedules of bortezomib and dexamethasone were synergistic, although pretreatment with dexamethasone resulted in additive interactions. Effects of combinations of bortezomib and TRAIL were generally additive. Thus, bortezomib represents a promising potential therapy for the treatment of PEL.

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Section: Drug Interactions Between Bortezomib and Trailsupporting

confidence: 91%

Section: Drug Interactions Between Bortezomib and Trailmentioning

confidence: 99%

Antitumor effects of bortezomib (PS-341) on primary effusion lymphomas

Sun

Fisher

et al. 2004

Leukemia

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“…As shown in Table 1 Kumar et al, 2001;Mitsiades et al, 2001). Since IFNs were reported to induce TRAIL in other cell systems Griffith et al, 1999;Langaas et al, 2001;Oshima et al, 2001;Shin et al, 2001;Toomey et al, 2001), we investigated whether TRAIL induction participated in IFNg-, IFNg/IFNa-or IFNg/TNFainduced SK-N-MC cell death. Figure 1a shows the kinetics of TRAIL mRNA induction, in response to stimulation with IFNg alone or in combination with IFNa or TNFa.…”

Section: Resultsmentioning

confidence: 99%

Type I interferon and TNFα cooperate with type II interferon for TRAIL induction and triggering of apoptosis in SK-N-MC EWING tumor cells

Abadie

Besançon

2004

Oncogene

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Ewing's sarcoma is the second most common human bone tumor in childhood. Here, we investigated the sensitivity of the Ewing tumor cell line, SK-N-MC, to the apoptotic effect of type I (IFNa) and type II (IFNc) interferons and TNFa. We demonstrate that although IFNa and TNFa alone are unable to induce cell death, they act in synergy with IFNc to induce SK-N-MC cell apoptosis. The synergistic induction of apoptosis correlated with the synergistic induction of TNFa-related apoptosis-inducing ligand (TRAIL) mRNA and TRAIL protein synthesis as well as of TRAIL secretion. Preparations of inducer-free supernatants from SK-N-MC cells stimulated with combinations of cytokines were shown to be cytotoxic for untreated SK-N-MC cells. This cytotoxicity was partially inhibited by addition of TRAILR2/Fc fusion protein, indicating that the secreted TRAIL mediates, at least in part, the apoptotic effect displayed by the supernatants of stimulated SK-N-MC cells. We have shown that the presence of IFNc is required to allow the sustained expression of IRF1 in SK-N-MC cells stimulated by addition of IFNa or TNFa suggesting that IRF1 plays a role in the synergistic induction of apoptosis by combinations of cytokines. Furthermore, we have shown that inhibition of NF-jB activation contributes to the IFNc-mediated sensitization to the apoptotic effect of TNFa. To our knowledge, this is the first report showing that interferon/cytokine combinations are able to induce TRAIL gene expression and TRAIL protein synthesis and secretion in Ewing sarcoma-derived cells. We believe that the observations reported here might contribute to the development of alternative new approaches to the treatment of Ewing tumors resistant to conventional therapy.

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“…Several investigators have recently reported that IFN-a/b stimulates the expression of TRAIL in T cells or dendritic cells, resulting in upregulation of their cytotoxic activities (Fanger et al, 1999;Kayagaki et al, 1999), and that the apoptosis observed in several cancer cells susceptible to IFN-a/b is mediated by induction of endogenous TRAIL in these cells (Chawla-Sarkar et al, 2001;Chen et al, 2001;Toomey et al, 2001). Taken together, these findings suggest that IFN-a/b may, at least in part, exhibit its antitumor activity through induction of TRAIL.…”

Section: Introductionmentioning

confidence: 86%

Interferon-α sensitizes human hepatoma cells to TRAIL-induced apoptosis through DR5 upregulation and NF-κB inactivation

et al. 2003

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Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF superfamily, induces apoptosis in a variety of cancer cells with little or no effect on normal cells. Human hepatoma cells, however, are resistant to TRAIL-induced apoptosis. Since interferon-a (IFN-a) is capable of enhancing TNF-ainduced apoptosis in certain cancer cells, we evaluated the effect of IFN-a on TRAIL-induced apoptosis of human hepatoma cells. IFN-a pretreatment enhanced TRAILinduced apoptosis of HuH-7 and Hep3B cells, in which IFN-a upregulated the expression of DR5, a death receptor of TRAIL, and downregulated the expression of survivin, which has an antiapoptotic function. In contrast, IFN-a did not enhance TRAIL-induced apoptosis of HepG2 cells, in which expression of DR5 and survivin was not affected by IFN-a. On the other hand, TRAIL activated NF-jB composed of RelA-p50 heterodimer, a key transcription factor regulating cell survival, in HuH-7 and HepG2 cells. However, IFN-a pretreatment repressed the TRAIL-mediated activation of NF-jB and decreased its transcriptional activity in HuH-7 but not in HepG2 cells. Moreover, IFN-a pretreatment clearly augmented TRAIL-mediated caspase-8 activation in HuH-7 cells. Our results suggest that IFN-a could sensitize certain human hepatoma cells to TRAIL-induced apoptosis by stimulating its death signaling and by repressing the survival function in these cells.

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Induction of a TRAIL mediated suicide program by interferon alpha in primary effusion lymphoma

Cited by 62 publications

References 43 publications

Antitumor effects of bortezomib (PS-341) on primary effusion lymphomas

Antitumor effects of bortezomib (PS-341) on primary effusion lymphomas

Type I interferon and TNFα cooperate with type II interferon for TRAIL induction and triggering of apoptosis in SK-N-MC EWING tumor cells

Interferon-α sensitizes human hepatoma cells to TRAIL-induced apoptosis through DR5 upregulation and NF-κB inactivation

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