BID is cleaved by caspase-8 within a native complex on the mitochondrial membrane

Schug, Zachary T.; Gonzalvez, François; Houtkooper, Riekelt H.; Vaz, Frédéric M.; Gottlieb, Eyal

doi:10.1038/cdd.2010.135

Cited by 152 publications

(117 citation statements)

References 36 publications

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“…Bid was identified as the preferred substrate of caspase-8 in vitro (30). It was previously reported that TRAIL induces the formation of an active caspase-8/tBid complex on the surface of the mitochondria, and thus activates the mitochondrial apoptotic pathway (31). In the present study, downregulation of Bid was more pronounced compared with caspase-3 during DAPT/TRAIL apoptotic synergy, suggesting a preference for Bid in the DAPT/TRAIL apoptotic pathway.…”

Section: A B Csupporting

confidence: 58%

Inhibition of γ-secretase activity synergistically enhances tumour necrosis factor-related apoptosis-inducing ligand induced apoptosis in T-cell acute lymphoblastic leukemia cells via upregulation of death receptor 5

2016

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Abstract. T-cell acute lymphoblastic leukemia (T-ALL) is a rare and aggressive hematopoietic malignancy prone to relapse and drug resistance. Half of all T-ALL patients exhibit mutations in Notch1, which leads to aberrant Notch1 associated signaling cascades. Notch1 activation is mediated by the γ-secretase cleavage of the Notch1 receptor into the active intracellular domain of Notch1 (NCID). Clinical trials of γ-secretase small molecule inhibitors (GSIs) as single agents for the treatment of T-ALL have been unsuccessful. The present study demonstrated, using immunofluorescence and western blotting, that blocking γ-secretase activity in T-ALL cells with N- [(3,5-difluorophenyl) acetyl]-L-alanyl-2-phenyl] glycine-1,1-dimethylethyl ester (DAPT) downregulated NCID and upregulated the tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor 5 (DR5). Upregulation of DR5 restored the sensitivity of T-ALL cells to TRAIL. Combination index revealed that the combined treatment of DAPT and TRAIL synergistically enhanced apoptosis compared with treatment with either drug alone. TRAIL combined with the clinically evaluated γ-secretase inhibitor 3-[(1r, 4s)-4-(4-chlorophenylsulfonyl)-4-(2, 5-difluorophenyl) cyclohexyl] propanoic acid (MK-0752) also significantly enhanced TRAIL-induced cell death compared with either drug alone. DAPT/TRAIL apoptotic synergy was dependent on the extrinsic apoptotic pathway and was associated with a decrease in BH3 interacting-domain death agonist and x-linked inhibitor of apoptosis. In conclusion, γ-secretase inhibition represents a potential therapeutic strategy to overcome TRAIL resistance for the treatment of T-ALL.

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Section: A B Csupporting

confidence: 58%

Inhibition of γ-secretase activity synergistically enhances tumour necrosis factor-related apoptosis-inducing ligand induced apoptosis in T-cell acute lymphoblastic leukemia cells via upregulation of death receptor 5

2016

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“…However, TRAIL-mediated apoptosis can also induce the mitochondria-mediated apoptosis pathway through the implication of mitochondrial dysfunction and caspase-9 activation via the cleavage of Bid (BH3-interacting domain death agonist) protein into truncated Bid (tBid) by caspase-8. tBid is capable of inducing mitochondrial outer membrane permeabilisation (MOMP) in cells in which the ratio of pro-and anti-apoptotic Bcl-2 family members allows it to do so leading to mitochondrial dysfunction in TRAILtreated cancer cells, also found in Fas type II cancer cells (4)(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

Goniothalamin enhances TRAIL-induced apoptosis in colorectal cancer cells through DR5 upregulation and cFLIP downregulation

Sophonnithiprasert

Nilwarangkoon

Nakamura

et al. 2015

International Journal of Oncology

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Abstract. The combination of TNF-related apoptosis-inducing ligand (TRAIL) and bioactive compound to enhance apoptosis in TRAIL-resistant cancer is one of cancer treatment strategies. TRAIL possesses the unique capacity to selectively induce apoptosis in cancer cells both in vitro and in vivo with little effect on normal cells. Recent studies have reported that there are many TRAIL-resistant cancers. Thus, bioactive compounds that enhance cytotoxicity of TRAIL would be potential candidates for cancer therapeutic application. This study evaluated the cytotoxic and apoptosis induction upon combined treatment of TRAIL and goniothalamin, the natural styryl-lactone compound extracted from plant Goniothalamus spp., in LoVo cells. The results showed that a combination of goniothalamin and TRAIL enhanced caspase-dependent apoptosis induction in LoVo cells via both death receptor-and mitochondrial-mediated apoptosis pathways. In addition, goniothalamin enhanced TRAIL-induced apoptosis through increased death receptor DR5 expression and decreased anti-apoptotic regulator cFLIP. Interestingly, goniothalamin increased translocation of DR5 to cell surface and consequently contributed to the enhancement of TRAIL-induced apoptosis. In conclusion, this is the first report showing the combined treatment of goniothalamin and TRAIL was able to effectively enhance TRAIL-mediated apoptosis induction in TRAIL-refractory colorectal cancer, LoVo cells. Therefore, this study may offer a strategic cancer treatment against TRAIL-resistant cancers.

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“…T h e d e a t h r e c e p t o r p a t hway l i n k s t o t h e mitochondria-dependent pathway by the linker molecule Bid (13)(14)(15). In previous studies, it was reported that the cleavage of Bid by caspase-8 triggered cytochrome c release from the mitochondria to the cell cytosol followed by activation of the caspase cascade with caspase-9 and caspase-3, and PARP cleavage (36,38).…”

Section: Discussionmentioning

confidence: 99%

“…The cytosolic Bid is cleaved by the activated caspase-8 to generate the truncated form of Bid, which translocates to the mitochondria and mediates cytochrome c release via direct interaction with Bcl-2 homologous antagonist killer and Bcl-2-associated protein. This mechanistic link apparently amplifies the apoptosis signal following death receptor activation by activating downstream effector caspases (13)(14)(15). Effector caspases, including caspase-3 and caspase-7, are responsible for the cleavage of cellular proteins such as poly(ADP-ribose) polymerase (PARP), which are involved in DNA repair and programmed cell death (16).…”

Section: Ethanolic Extract Of Thevetia Peruviana Flowers Enhances Tnfmentioning

confidence: 99%

Ethanolic extract of Thevetia peruviana flowers enhances TNF-α and TRAIL-induced apoptosis of human cervical cancer cells via intrinsic and extrinsic pathways

2017

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Abstract. Tumor necrosis factor-α (TNF-α) and TNF-related apoptosis-inducing ligand (TRAIL) are promising candidates for cancer treatment due to their ability to induce apoptosis through death receptor stimulation. However, their usage may be limited due to the resistance of cancer cells to TNF-α-and TRAIL-induced apoptosis. Currently, there is interest in screening for natural products that can sensitize cancer cells to TNF-α-and TRAIL-induced apoptosis for their use in combination with TNF-α or TRAIL. It was previously reported that the bark extract of Thevetia peruviana showed a reversal effect on TRAIL-resistance in human gastric adenocarcinoma cell lines. In the present study, the effects of the ethanolic extract of T. peruviana flowers on TNF-α-and TRAIL-induced apoptosis of human cervical cancer HeLa cells were investigated in vitro by determining cell viability and apoptosis using a WST-1 cell proliferation assay and immunoblot analysis, respectively. The ethanolic extract of T. peruviana flowers promoted TNF-α and TRAIL-mediated cell death through the activation of the caspase cascade, poly(ADP-ribose) polymerase and BH3-interacting domain death agonist cleavage. Combined treatment using the extract plus TNF-α resulted in downregulation of anti-apoptotic protein, including myeloid cell leukemia sequence-1, B-cell lymphoma-extra large (Bcl-XL), X-linked inhibitor of apoptosis protein and survivin, while the combined treatment with TRAIL downregulated Bcl-XL. Thus, the ethanolic extract of T. peruviana flowers has potential in sensitizing the TNF-α-and TRAIL-induced apoptosis of HeLa cells via the intrinsic and extrinsic pathways. IntroductionChemotherapy is one of the major standard treatments that is beneficial for numerous cancer types due to its efficient induction of tumor cell death by apoptosis. At present, the cancer resistance of chemotherapeutic drugs is a major drawback that leads to the failure of cancer treatments. Chemotherapeutic drugs eliminate tumor cells by the induction of apoptosis via two distinct pathways, which act through the mitochondria (intrinsic signaling pathway) or through death receptors on the cell surface (extrinsic signaling pathway) (1). Induction of apoptosis via the intrinsic signaling pathway is initiated by severe cell stress, including DNA damage, mitotic catastrophe, hypoxia and cell cycle checkpoint defects. The majority of conventional chemotherapeutic drugs trigger DNA damage and induce apoptosis via the intrinsic signaling pathway by the activation of tumor suppressor protein, p53, which leads to the breakdown of mitochondrial membrane and the release of cytochrome c into the cytosol. Cytochrome c binds to the adaptor apoptotic protease activating factor 1, forming an apoptosome. The apoptosome subsequently activates caspase-9 and caspase-3, which results in the cleavage of death substrates (2-4). Defects in intrinsic apoptosis signal transduction, such as the mutation of p53, contributes to the chemotherapeutic drug resistance of cancer (5,6). The extrinsic pa...

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BID is cleaved by caspase-8 within a native complex on the mitochondrial membrane

Cited by 152 publications

References 36 publications

Inhibition of γ-secretase activity synergistically enhances tumour necrosis factor-related apoptosis-inducing ligand induced apoptosis in T-cell acute lymphoblastic leukemia cells via upregulation of death receptor 5

Inhibition of γ-secretase activity synergistically enhances tumour necrosis factor-related apoptosis-inducing ligand induced apoptosis in T-cell acute lymphoblastic leukemia cells via upregulation of death receptor 5

Goniothalamin enhances TRAIL-induced apoptosis in colorectal cancer cells through DR5 upregulation and cFLIP downregulation

Ethanolic extract of Thevetia peruviana flowers enhances TNF-α and TRAIL-induced apoptosis of human cervical cancer cells via intrinsic and extrinsic pathways

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