Liposome-bound TRAIL induces superior DR5 clustering and enhanced DISC recruitment in histiocytic lymphoma U937 cells

Miguel, Diego de; Gallego-Lleyda, Ana; Anel, Alberto; Martínez-Lostao, Luis

doi:10.1016/j.leukres.2015.03.019

Cited by 45 publications

(54 citation statements)

References 38 publications

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“…Through its binding to its cognate agonistic receptors, namely, DR4 and DR5, TRAIL is able to induce apoptosis in malignant cells without harming healthy cells. Our findings are in line with other reports that combination of TRAIL as a recombinant protein (De Miguel et al, ; De Miguel et al, ; Kim et al, ; Lim et al, ; Kim et al, ; Kim et al, ; Guo et al, ; Guo et al, ; Guo et al, ; Muller et al, ) and a cDNA‐encoding TRAIL (Miao et al, ; Sun et al, ) with a large variety of carrier NPs improves its therapeutic potential. Preliminary in vivo results on the use of such hybrids are very encouraging, although the drug was always injected into the tumors directly (Perlstein et al, ; Miao et al, ; Riehle et al, ) and not intravenously.…”

Section: Discussionsupporting

confidence: 92%

Coupling tumor necrosis factor‐related apoptosis‐inducing ligand to iron oxide nanoparticles increases its apoptotic activity on HCT116 and HepG2 malignant cells: effect of magnetic core size

Belkahla

Haque

Revzin

et al. 2019

J of Interdiscip Nanomed

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Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been considered as a potential anticancer agent owing to its selectivity for malignant cells. However, its clinical use remains limited because of its poor efficacy. Attempts to increase its antitumor activity include, among others, its functionalization by nanoparticles (NPs). In the present study, TRAIL was grafted onto magnetic spinel iron oxide NPs of defined core size, 10 and 100 nm on average, to see whether the size of the resulting nanovectors, NV10 and NV100, respectively, might affect TRAIL efficacy and selectivity. Apoptosis induced by NV10 and NV100 was higher than by TRAIL alone in both HCT116 and HepG2 cells. At equimolar concentrations, neither the nanovectors nor the corresponding NPs displayed cytotoxicity towards normal primary hepatocytes or TRAIL receptor-deficient HCT116 cells. NV100 exhibited superior proapoptotic activity than NV10, as evidenced by methylene blue and annexin V staining. Consistently, both caspase activation and TRAIL deathinduced signaling complex formation, as assessed by immunoblot analysis, were found to be increased in cells treated with NV100 as compared with NV10 or TRAIL alone. These results suggest that the size of NPs is important when TRAIL is vectorized for cancer therapy.

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Section: Discussionsupporting

confidence: 92%

Coupling tumor necrosis factor‐related apoptosis‐inducing ligand to iron oxide nanoparticles increases its apoptotic activity on HCT116 and HepG2 malignant cells: effect of magnetic core size

Belkahla

Haque

Revzin

et al. 2019

J of Interdiscip Nanomed

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“…In fact, co-treatment of soluble TRAIL with an agonistic anti-DR5 antibody allowed an enhanced DR5 activation mediated by the artificial cross-linking of this receptor facilitated by the agonistic antibody [55,56]. We previously demonstrated that the enhanced cytotoxicity showed by LUV-TRAIL in human leukemic cells relied on their higher efficiency for promoting DR5 clustering leading to a higher DISC recruitment [41]. In the present study, we wanted to corroborate this feature also in CRC cells.…”

Section: Discussionmentioning

confidence: 71%

“…In this line, our group previously demonstrated that human lymphocytes secrete TRAIL preferably associated with lipid vesicles called exosomes [35,36] Aiming to mimic this exosome-bound TRAIL, we generated the novel TRAIL formulation LUV-TRAIL, based on anchoring this death ligand on Large Unilamellar Vesicles (LUV) resembling these natural exosomes. LUV-TRAIL has been proved to be much more potent than soluble TRAIL both in haematological malignancies [37,38,41] and solid tumours [39,40]. Remarkably, the soluble version of TRAIL used in all those studies is virtually identical to the version used in clinical trials (Dulanermin®), which confers more significance to LUV-TRAIL improved efficiency.…”

Section: Discussionmentioning

confidence: 99%

“…We already demonstrated that LUV-TRAIL was more effective inducing apoptosis than soluble TRAIL against leukemia cells that presented resistance to soluble TRAIL and chemotherapeutic drugs [37,38] and also in epithelial-derived cancer cells [39,40]. This increased cytotoxicity induced by LUV-TRAIL was due to a superior DR5 activation, which led to an enhanced DISC recruitment [40,41].…”

Section: Introductionmentioning

confidence: 99%

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High-order TRAIL oligomer formation in TRAIL-coated lipid nanoparticles enhances DR5 cross-linking and increases antitumour effect against colon cancer

et al. 2016

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During the last years, a great effort has been invested into developing new TRAIL formulations with increased bioactivity, trying to overcome the resistance to conventional soluble TRAIL (sTRAIL) exhibited by many primary tumours. In our group, we have generated artificial lipid nanoparticles decorated with sTRAIL (LUV-TRAIL), emulating the physiological TRAIL-containing exosomes by which T-cells release TRAIL upon activation. We already demonstrated that LUV-TRAIL has greater cytotoxicity against both chemoresistant haematologic tumour cells and epithelial carcinoma cells compared to a form of sTRAIL similar to that used in clinical trials. In this study we have tested LUV-TRAIL in several human colon cancer cell lines with different sensitivity to sTRAIL. LUV-TRAIL significantly improved sTRAIL cytotoxicity in all colon cancer cell lines tested. Trying to ascertain the molecular mechanism by which LUV-TRAIL exhibited improved cytotoxicity, we demonstrated that TRAIL-coated lipid nanoparticles were able to activate DR5 more efficiently than sTRAIL, and this relied on LUV-TRAIL ability to promote DR5 clustering on the cell surface. Moreover, we show that TRAIL molecules are arranged in higher order oligomers only in LUV-TRAIL, which may explain their enhanced DR5 clustering ability. Finally, LUV-TRAIL showed significantly better antitumour activity than sTRAIL in an in vivo model using HCT-116 xenograft tumours in nude mice, validating its potential clinical application.

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“…The DISC functions as the essential platform for TRAIL to activate caspase‐8 and subsequent apoptosis (De Miguel et al ., 2015). However, another complex known as the preligand assembly complex (PLAC), containing TNF‐α‐induced protein 3 (TNFAIP3), receptor‐interacting protein (RIP), DR5, and TRAF2, has been found in glioblastoma.…”

Section: Introductionmentioning

confidence: 99%

DR5‐Cbl‐b/c‐Cbl‐TRAF2 complex inhibits TRAIL‐induced apoptosis by promoting TRAF2‐mediated polyubiquitination of caspase‐8 in gastric cancer cells

Zhang

et al. 2017

Molecular Oncology

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Ubiquitination of caspase‐8 regulates TNF‐related apoptosis‐inducing ligand (TRAIL) sensitivity in cancer cells, and the preligand assembly complex plays a role in caspase‐8 polyubiquitination. However, whether such a complex exists in gastric cancer cells and its role in TRAIL‐triggered apoptosis is unclear. In this study, DR5, casitas B‐lineage lymphoma‐b (Cbl‐b)/c‐Cbl, and TRAF2 formed a complex in TRAIL‐resistant gastric cancer cells, and Cbl‐b and c‐Cbl were the critical adaptors linking DR5 and TRAF2. Treatment with TRAIL induced caspase‐8 translocation into the DR5‐Cbl‐b/c‐Cbl‐TRAF2 complex to interact with TRAF2, which then mediated the K48‐linked polyubiquitination of caspase‐8. The proteasome inhibitor bortezomib markedly enriched the p43/41 products of caspase‐8 activated by TRAIL, indicating proteasomal degradation of caspase‐8. Moreover, TRAF2 knockdown prevented the polyubiquitination of caspase‐8 and thus increased TRAIL sensitivity. In addition, the inhibition of Cbl‐b or c‐Cbl expression and overexpression of miR‐141 targeting Cbl‐b and c‐Cbl partially reversed TRAIL resistance by inhibiting the interaction between TRAF2 and caspase‐8 and the subsequent polyubiquitination of caspase‐8. These results indicate that the DR5‐Cbl‐b/c‐Cbl‐TRAF2 complex inhibited TRAIL‐induced apoptosis by promoting TRAF2‐mediated polyubiquitination of caspase‐8 in gastric cancer cells.

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Liposome-bound TRAIL induces superior DR5 clustering and enhanced DISC recruitment in histiocytic lymphoma U937 cells

Cited by 45 publications

References 38 publications

Coupling tumor necrosis factor‐related apoptosis‐inducing ligand to iron oxide nanoparticles increases its apoptotic activity on HCT116 and HepG2 malignant cells: effect of magnetic core size

Coupling tumor necrosis factor‐related apoptosis‐inducing ligand to iron oxide nanoparticles increases its apoptotic activity on HCT116 and HepG2 malignant cells: effect of magnetic core size

High-order TRAIL oligomer formation in TRAIL-coated lipid nanoparticles enhances DR5 cross-linking and increases antitumour effect against colon cancer

DR5‐Cbl‐b/c‐Cbl‐TRAF2 complex inhibits TRAIL‐induced apoptosis by promoting TRAF2‐mediated polyubiquitination of caspase‐8 in gastric cancer cells

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