Caspases activation in hyperthermia-induced stimulation of TRAIL apoptosis

Moulin, Maryline; Arrigo, André‐Patrick

doi:10.1007/s12192-008-0027-3

Cited by 14 publications

(9 citation statements)

References 39 publications

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“…Hyperthermia restores TRAIL-induced apoptosis in tumor cells 17 , 23 , 24 but not in normal cells. 25 In line with these findings, incubating resistant cancer cell lines of various origin for 1 h at 42 °C (HS) in the presence of TRAIL followed by subsequent incubation at 37 °C for 5 h ( Figure 1a ), significantly increased apoptosis triggered by TRAIL as compared with a 6 h incubation time at 37 °C ( Figure 1b ).…”

Section: Resultsmentioning

confidence: 96%

Hyperthermia restores apoptosis induced by death receptors through aggregation-induced c-FLIP cytosolic depletion

2015

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TRAIL is involved in immune tumor surveillance and is considered a promising anti-cancer agent owing to its limited side effects on healthy cells. However, some cancer cells display resistance, or become resistant to TRAIL-induced cell death. Hyperthermia can enhance sensitivity to TRAIL-induced cell death in various resistant cancer cell lines, including lung, breast, colon or prostate carcinomas. Mild heat shock treatment has been proposed to restore Fas ligand or TRAIL-induced apoptosis through c-FLIP degradation or the mitochondrial pathway. We demonstrate here that neither the mitochondria nor c-FLIP degradation are required for TRAIL-induced cell death restoration during hyperthermia. Our data provide evidence that insolubilization of c-FLIP, alone, is sufficient to enhance apoptosis induced by death receptors. Hyperthermia induced c-FLIP depletion from the cytosolic fraction, without apparent degradation, thereby preventing c-FLIP recruitment to the TRAIL DISC and allowing efficient caspase-8 cleavage and apoptosis. Hyperthermia-induced c-FLIP depletion was independent of c-FLIP DED2 FL chain assembly motif or ubiquitination-mediated c-FLIP degradation, as assessed using c-FLIP point mutants on lysine 167 and 195 or threonine 166, a phosphorylation site known to regulate ubiquitination of c-FLIP. Rather, c-FLIP depletion was associated with aggregation, because addition of glycerol not only prevented the loss of c-FLIP from the cytosol but also enabled c-FLIP recruitment within the TRAIL DISC, thus inhibiting TRAIL-induced apoptosis during hyperthermia. Altogether our results demonstrate that c-FLIP is a thermosensitive protein whose targeting by hyperthermia allows restoration of apoptosis induced by TNF ligands, including TRAIL. Our findings suggest that combining TRAIL agonists with whole-body or localized hyperthermia may be an interesting approach in cancer therapy.

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Section: Resultsmentioning

confidence: 96%

Hyperthermia restores apoptosis induced by death receptors through aggregation-induced c-FLIP cytosolic depletion

2015

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“…We have already established the magnetocalorimetric properties of coated (Hai et al, ) and uncoated (Hanini et al, ) polyol‐made iron oxide NPs and their ability to induce malignant cell apoptosis by hyperthermia, opening up synergetic therapeutic opportunities. Indeed, a local rise of temperature under an applied AC magnetic field can sensitize tumor cells to TRAIL‐induced apoptosis (Morle et al, ; Moulin and Arrigo, ; Moulin et al, ; Yoo et al, ) as it can compensate the lack of efficiency of TRAIL in certain resistant cells (Song et al, ).…”

Section: Discussionmentioning

confidence: 99%

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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“…These results are consistent with recent reports describing caspase activation during HS even if the apical signalization (apical protease or caspase 2) is still a matter of debate. 34,35,45 However, heat sensitivity of p65-depleted cells was still observed following z-VAD-fmk treatment, suggesting that this phenomenon is caspase-independent. Hence, NFκB mediated cell survival after HS is not due to its anti-apoptotic functions.…”

Section: Downloaded By [Chinese University Of Hong Kong] At 06:27 08 mentioning

confidence: 99%

Autophagy activation by NFκB is essential for cell survival after heat shock

et al. 2009

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The heat shock response is a widely described defense mechanism during which the preferential expression of heat shock proteins (Hsps) helps the cell to recover from thermal damages such as protein denaturation/aggregation. We have previously reported that NFkappaB transcription factor is activated during the recovery period after heat shock. In this study, we analyze the consequences of NFkappaB activation during heat shock recovery, by comparing the heat shock response of NFkappaB competent and incompetent (p65/RelA-depleted) cells. We demonstrate for the first time that NFkappaB plays a major and crucial role during the heat shock response by activating autophagy, which increases survival of heat-treated cells. Indeed, we observed that autophagy is not activated during heat shock recovery and cell death is strongly increased in NFkappaB incompetent cells. Moreover, if autophagy is artificially induced in these cells, the cytotoxicity of heat shock is turned back to normal. We show that despite a post-heat shock increase of Beclin 1 level in NFkappaB competent cells, neither Beclin 1/class III PI3K complex, Bcl(2)/Bcl-X(L) nor mTOR kinase are NFkappaB targets whose modulation of expression could be responsible for NFkappaB activation of autophagy during heat shock recovery. In contrast, we demonstrate that aberrantly folded/aggregated proteins are prime events in the signaling pathway leading to NFkappaB mediated autophagy after heat shock. Hence, our findings demonstrate that NFkappaB-induced autophagy during heat shock recovery is an additional cell response to HS-induced protein denaturation/aggregation; this mechanism increases cell survival, probably through clearance of irreversibly damaged proteins.

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Caspases activation in hyperthermia-induced stimulation of TRAIL apoptosis

Cited by 14 publications

References 39 publications

Hyperthermia restores apoptosis induced by death receptors through aggregation-induced c-FLIP cytosolic depletion

Hyperthermia restores apoptosis induced by death receptors through aggregation-induced c-FLIP cytosolic depletion

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

Autophagy activation by NFκB is essential for cell survival after heat shock

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