scholarly journals Nitrosylcobalamin Promotes Cell Death via S Nitrosylation of Apo2L/TRAIL Receptor DR4

2006 ◽  
Vol 26 (15) ◽  
pp. 5588-5594 ◽  
Author(s):  
Zhuo Tang ◽  
Joseph A. Bauer ◽  
Bei Morrison ◽  
Daniel J. Lindner
Keyword(s):  
Cell Death ◽  
Cell Lines ◽  
Human Cancer ◽  
Death Receptor ◽  
The Other ◽  
Caspase 8 ◽  
Trail Receptor ◽  
Wild Type ◽  
Human Cancer Cell Lines ◽  
Induced Apoptosis

ABSTRACT We have previously demonstrated that nitrosylcobalamin (NO-Cbl), an analogue of vitamin B12 that delivers nitric oxide (NO), had potent antiproliferative activity against several human cancer cell lines. NO-Cbl induced apoptosis via a death receptor/caspase-8 pathway. In this study, we demonstrate that a functional Apo2L/TRAIL receptor was necessary for the induction of cell death by NO-Cbl. Furthermore, the Apo2L/TRAIL death receptor DR4 (TRAIL R1) was S nitrosylated following NO-Cbl treatment. Human melanoma (A375), renal carcinoma (ACHN), and ovarian carcinoma (NIH-OVCAR-3) cells were treated with NO-Cbl and subjected to the biotin switch assay; S-nitrosylated DR4 was detected in all three cell lines. NO-Cbl treatment did not cause S nitrosylation of DR5. The seven cysteine residues located in the cytoplasmic domain of DR4 were individually point mutated to alanines. NIH-OVCAR-3 cells expressing the DR4 C336A mutation lacked S nitrosylation following NO-Cbl treatment. Overexpression of wild-type DR4 sensitized cells to growth inhibition by NO-Cbl. Cells expressing the DR4 C336A mutant were more resistant to NO-Cbl and Apo2L/TRAIL than were the other six C-A mutations or wild-type cells. The C336A mutant also displayed blunted caspase-8 enzymatic activity following NO-Cbl treatment compared to the other mutants. Thus, DR4 residue C336 becomes S nitrosylated and promotes apoptosis following NO-Cbl treatment.

scholarly journals Caspase-8 deficiency induces a switch from TLR3 induced apoptosis to lysosomal cell death in neuroblastoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marie-Anaïs Locquet ◽  
Gabriel Ichim ◽  
Joseph Bisaccia ◽  
Aurelie Dutour ◽  
Serge Lebecque ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Neuroblastoma Cell ◽  
Death Receptor ◽  
Neuroblastoma Cell Line ◽  
Caspase 8 ◽  
Caspase Activation ◽  
Extrinsic Pathway ◽  
Lysosomal Membrane Permeabilization ◽  
Induced Apoptosis

AbstractIn cancer cells only, TLR3 acquires death receptor properties by efficiently triggering the extrinsic pathway of apoptosis with Caspase-8 as apical protease. Here, we demonstrate that in the absence of Caspase-8, activation of TLR3 can trigger a form of programmed cell death, which is distinct from classical apoptosis. When TLR3 was activated in the Caspase-8 negative neuroblastoma cell line SH-SY5Y, cell death was accompanied by lysosomal permeabilization. Despite caspases being activated, lysosomal permeabilization as well as cell death were not affected by blocking caspase-activity, positioning lysosomal membrane permeabilization (LMP) upstream of caspase activation. Taken together, our data suggest that LMP with its deadly consequences represents a “default” death mechanism in cancer cells, when Caspase-8 is absent and apoptosis cannot be induced.

High-risk HPV-positive human cancer cell lines show different sensitivity to cisplatin-induced apoptosis correlated with the p21Waf1/Cip1 level

1996 ◽  
Vol 108 (1) ◽  
pp. 15-23 ◽  
Author(s):  
Kohsei Funaoka ◽  
Masanobu Shindoh ◽  
Toshiharu Yamashita ◽  
Kei Fujinaga ◽  
Akira Amemiya ◽  
...  
Keyword(s):  
High Risk ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Human Cancer Cell ◽  
Human Cancer Cell Lines ◽  
Induced Apoptosis ◽  
High Risk Hpv

scholarly journals Upstream Regulatory Role for XIAP in Receptor-Mediated Apoptosis

2004 ◽  
Vol 24 (16) ◽  
pp. 7003-7014 ◽  
Author(s):  
John C. Wilkinson ◽  
Enrique Cepero ◽  
Lawrence H. Boise ◽  
Colin S. Duckett
Keyword(s):  
Cell Death ◽  
Cell Lines ◽  
Death Receptor ◽  
Full Length ◽  
Proliferative Capacity ◽  
Term Survival ◽  
Truncation Mutant ◽  
Short And Long Term ◽  
Induced Apoptosis

ABSTRACT X-linked inhibitor of apoptosis (XIAP) is an endogenous inhibitor of cell death that functions by suppressing caspases 3, 7, and 9. Here we describe the establishment of Jurkat-derived cell lines stably overexpressing either full-length XIAP or a truncation mutant of XIAP that can only inhibit caspase 9. Characterization of these cell lines revealed that following CD95 activation full-length XIAP supported both short- and long-term survival as well as proliferative capacity, in contrast to the truncation mutant but similar to Bcl-xL. Full-length XIAP was also able to inhibit CD95-mediated caspase 3 processing and activation, the mitochondrial release of cytochrome c and Smac/DIABLO, and the loss of mitochondrial membrane potential, whereas the XIAP truncation mutant failed to prevent any of these cell death events. Finally, suppression of XIAP levels by RNA interference sensitized Bcl-xL-overexpressing cells to death receptor-induced apoptosis. These data demonstrate for the first time that full-length XIAP inhibits caspase activation required for mitochondrial amplification of death receptor signals and that, by acting upstream of mitochondrial activation, XIAP supports the long-term proliferative capacity of cells following CD95 stimulation.

scholarly journals Comparison of Cellular Death Pathways after mTHPC-mediated Photodynamic Therapy (PDT) in Five Human Cancer Cell Lines

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 702 ◽  
Author(s):  
Carsten Lange ◽  
Christiane Lehmann ◽  
Martin Mahler ◽  
Patrick J. Bednarski
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Photodynamic Therapy ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Human Cancer Cell ◽  
Human Cancer Cell Lines ◽  
Cell Death Mechanisms

One of the most promising photosensitizers (PS) used in photodynamic therapy (PDT) is the porphyrin derivative 5,10,15,20-tetra(m-hydroxyphenyl)chlorin (mTHPC, temoporfin), marketed in Europe under the trade name Foscan®. A set of five human cancer cell lines from head and neck and other PDT-relevant tissues was used to investigate oxidative stress and underlying cell death mechanisms of mTHPC-mediated PDT in vitro. Cells were treated with mTHPC in equitoxic concentrations and illuminated with light doses of 1.8–7.0 J/cm2 and harvested immediately, 6, 24, or 48 h post illumination for analyses. Our results confirm the induction of oxidative stress after mTHPC-based PDT by detecting a total loss of mitochondrial membrane potential (Δψm) and increased formation of ROS. However, lipid peroxidation (LPO) and loss of cell membrane integrity play only a minor role in cell death in most cell lines. Based on our results, apoptosis is the predominant death mechanism following mTHPC-mediated PDT. Autophagy can occur in parallel to apoptosis or the former can be dominant first, yet ultimately leading to autophagy-associated apoptosis. The death of the cells is in some cases accompanied by DNA fragmentation and a G2/M phase arrest. In general, the overall phototoxic effects and the concentrations as well as the time to establish these effects varies between cell lines, suggesting that the cancer cells are not all dying by one defined mechanism, but rather succumb to an individual interplay of different cell death mechanisms. Besides the evaluation of the underlying cell death mechanisms, we focused on the comparison of results in a set of five identically treated cell lines in this study. Although cells were treated under equitoxic conditions and PDT acts via a rather unspecific ROS formation, very heterogeneous results were obtained with different cell lines. This study shows that general conclusions after PDT in vitro require testing on several cell lines to be reliable, which has too often been ignored in the past.

Ectopic expression of Flt3 kinase inhibits proliferation and promotes cell death in different human cancer cell lines

2012 ◽  
Vol 28 (4) ◽  
pp. 201-212 ◽  
Author(s):  
Eystein Oveland ◽  
Line Wergeland ◽  
Randi Hovland ◽  
James B. Lorens ◽  
Bjørn Tore Gjertsen ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Ectopic Expression ◽  
Cancer Cell Lines ◽  
Human Cancer Cell ◽  
Human Cancer Cell Lines

scholarly journals Dihydroartemisinin-Transferrin Adducts Enhance TRAIL-Induced Apoptosis in Triple-Negative Breast Cancer in a P53-Independent and ROS-Dependent Manner

2022 ◽  
Vol 11 ◽  
Author(s):  
Xinyu Zhou ◽  
Abel Soto-Gamez ◽  
Fleur Nijdam ◽  
Rita Setroikromo ◽  
Wim J. Quax
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Cell Lines ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Breast Cancer Subtype ◽  
Death Receptor ◽  
Dependent Manner ◽  
Tnbc Cell ◽  
Induced Apoptosis

Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer subtype independent of estrogen receptor, progesterone receptor, or human epidermal growth factor receptor 2. It has a poor prognosis and high recurrence. Due to its limited treatment options in the clinic, novel therapies are urgently needed. Single treatment with the death receptor ligand TRAIL was shown to be poorly effective. Recently, we have shown that artemisinin derivatives enhance TRAIL-induced apoptosis in colon cancer cells. Here, we utilized transferrin (TF) to enhance the effectiveness of dihydroartemisinin (DHA) in inducing cell death in TNBC cell lines (MDA-MB-231, MDA-MB-436, MDA-MB-468 and BT549). We found that the combination of DHA-TF and the death receptor 5-specific TRAIL variant DHER leads to an increase in DR5 expression in all four TNBC cell lines, while higher cytotoxicity was observed in MDA-MB-231, and MDA-MB-436. All the data point to the finding that DHA-TF stimulates cell death in TNBC cells, while the combination of DHA-TF with TRAIL variants will trigger more cell death in TRAIL-sensitive cells. Overall, DHA-TF in combination with TRAIL variants represents a potential novel combination therapy for triple-negative breast cancer.

scholarly journals A putative PPAR beta/delta agonist induces cell death in human cancer cell lines

2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
David Kelly Strom ◽  
Dalon Li ◽  
Hanna Brinkman ◽  
Stephanie Gleason ◽  
Sarah Hershberger ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Human Cancer Cell ◽  
Human Cancer Cell Lines

scholarly journals Chemical Constituents of Equisetum Debile and their Cytotoxic Activity

2008 ◽  
Vol 3 (11) ◽  
pp. 1934578X0800301
Author(s):  
Tran Huy Thai ◽  
Nguyen Quang Hung ◽  
Chau Van Minh ◽  
Nguyen Xuan Cuong ◽  
Pham Hai Yen ◽  
...  
Keyword(s):  
Cell Lines ◽  
Human Cancer ◽  
Chemical Constituents ◽  
In Vitro Assay ◽  
The Other ◽  
Human Cancer Cell ◽  
Vitro Assay ◽  
Human Cancer Cell Lines ◽  
Aerial Parts

A new phenyl glycoside, equisetumoside D (1), was isolated from the aerial parts of Equisetum debile, along with equisetumoside B (2), dehydrovomifoliol (3), corchoionoside C (4), (-)-isolariciresinol-3a-O-β-D-glucopyranoside (5), and kaempferol 3-O-sophoroside-7-O-β-D-glucopyranoside (6). Their structures were elucidated by NMR spectroscopic and MS experiments. Compound 1 was found to be cytotoxic against both tested human cancer cell lines, hepatocellular carcinoma (Hep-G2, IC50: 1.12 μg/mL) and rhabdosarcoma (RD, IC50: 0.25 μg/mL), while the other compounds showed no activity against these cell lines by in vitro assay.

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