Paraptosis

Khalili, Maryam; Radosevich, James A.

doi:10.1002/9781119432463.ch16

Cited by 6 publications

(7 citation statements)

References 45 publications

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“…It is known that mitochondrial swelling and cytoplasmic vacuolation are paraptosis hallmarks. [ 39 , 40 ] The fact that no emission was observed from the cytoplasmic vacuolization with an inverted microscope, suggest, once again, mitochondria and in particular swollen mitochondria, as source of the bright emissive round pattern.…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, paraptosis is an independent caspases mechanism that displays mitochondrial swelling and produces cytoplasmatic vacuolation mainly derived from endoplasmic reticulum. [ 39 , 40 ] Despite several of these characteristics are in agreement with our observations, we identified cellular blebbing and apoptotic bodies in microscopy evaluation (black arrows in Figures S20 and S21) as well as annexin V labelling in flow cytometry analysis at 48 h of treatment but not at 24 h. Similarly, a study with an Alzheimer's disease cell model showed the presence of paraptotic cells at 24 h and with an increase in culture time, the presence of apoptotic cells after 48 h. In addition, a decrease in the expression levels of Bcl‐2 and Bax overexpression was observed at 48 and 72 h, suggesting that paraptosis finally unleashes mitochondrial apoptotic pathway. [41] Therefore, in the present case, it can be concluded that complexes 1 and 4 mediate paraptosis with subsequent apoptotic cell death.…”

Section: Resultsmentioning

confidence: 99%

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Multifunctional Heterometallic Ir^III−Au^I Probes as Promising Anticancer and Antiangiogenic Agents

Redrado

Benedi

Marzo

et al. 2021

Chemistry A European J

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A new class of emissive cyclometallated IrIII−AuI complexes with a bis(diphenylphosphino) methanide bridging ligand was successfully synthesised from the diphosphino complex [Ir(N^C)2(dppm)]+ (1). The different gold ancillary ligand, a triphenylphosphine (2), a chloride (3) or a thiocytosine (4) did not reveal any significant effect on the photophysical properties, which are mainly due to metal‐to‐ligand charge‐transfer (3MLCT) transitions based on IrIII. However, the AuI fragment, along with the ancillary ligand, seemed crucial for the bioactivity in A549 lung carcinoma cells versus endothelial cells. Both cell types display variable sensitivities to the complexes (IC50=0.6–3.5 μM). The apoptotic pathway is activated in all cases, and paraptotic cell death seems to take place at initial stages in A549 cells. Species 2–4 showed at least dual lysosomal and mitochondrial biodistribution in A549 cells, with an initial lysosomal localisation and a possible trafficking process between both organelles with time. The bimetallic IrIII−AuI complexes disrupted the mitochondrial transmembrane potential in A549 cells and increased reactive oxygen species (ROS) generation and thioredoxin reductase (TrxR) inhibition in comparison with that displayed by the monometallic complex 1. Angiogenic activity assays performed in endothelial cells revealed the promising antimetastatic potential of 1, 2 and 4.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Multifunctional Heterometallic Ir^III−Au^I Probes as Promising Anticancer and Antiangiogenic Agents

Redrado

Benedi

Marzo

et al. 2021

Chemistry A European J

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show abstract

Section: Discussionmentioning

confidence: 99%

“…Paraptosis is a mode of unique programmed cell death independent of caspases activation and lack of typical apoptotic features [ 81 ]. Additionally, cells undergoing paraptosis have an intact cell membrane, phosphatidylserine markers, extensive cytoplasmic vacuolation and swelled ER and mitochondria [ 81 ]. In this study, the microscopic observation revealed an interesting finding, whereby AnTT, γ-T3 and δ-T3 induced massive vacuole formation on SW1353 cells which may indicate activation of paraptosis or paraptosis-like cell death.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic Analysis of the Anticancer Effects of Annatto Tocotrienol, Delta-Tocotrienol and Gamma-Tocotrienol on Chondrosarcoma Cells

et al. 2022

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Previous studies have demonstrated the anticancer activities of tocotrienol on several types of cancer, but its effects on chondrosarcoma have never been investigated. Therefore, this study aims to determine the anticancer properties of annatto tocotrienol (AnTT), γ-tocotrienol (γ-T3) and δ-tocotrienol (δ-T3) on human chondrosarcoma SW1353 cells. Firstly, the MTT assay was performed to determine the half-maximal inhibitory concentration (IC50) of tocotrienol on SW1353 cells after 24 h treatment. The mode of cell death, cell cycle analysis and microscopic observation of tocotrienol-treated SW1353 cells were then conducted according to the respective IC50 values. Subsequently, RNAs were isolated from tocotrienol-treated cells and subjected to RNA sequencing and transcriptomic analysis. Differentially expressed genes were identified and then verified with a quantitative PCR. The current study demonstrated that AnTT, γ-T3 and δ-T3 induced G1 arrest on SW1353 cells in the early phase of treatment (24 h) which progressed to apoptosis upon 48 h of treatment. Furthermore, tocotrienol-treated SW1353 cells also demonstrated large cytoplasmic vacuolation. The subsequent transcriptomic analysis revealed upregulated signalling pathways in endoplasmic reticulum stress, unfolded protein response, autophagy and transcription upon tocotrienol treatment. In addition, several cell proliferation and cancer-related pathways, such as Hippo signalling pathway and Wnt signalling pathway were also significantly downregulated upon treatment. In conclusion, AnTT, γ-T3 and δ-T3 possess promising anticancer properties against chondrosarcoma cells and further study is required to confirm their effectiveness as adjuvant therapy for chondrosarcoma.

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“…Hence, there has been a growing interest in and demand for the discovery of drugs targeting alternative cell death modes other than apoptosis. Paraptosis is recently described as a form of programmed cell death (PCD), characterized by features distinct from apoptotic or autophagic cell death [ 4 ]. The hallmark of paraptosis is the formation of extensive cellular vacuolization, which is generated from either endoplasmic reticulum (ER) stress or mitochondria swelling [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Induction of Paraptotic Cell Death in Breast Cancer Cells by a Novel Pyrazolo[3,4-h]quinoline Derivative through ROS Production and Endoplasmic Reticulum Stress

Nguyen

Lee

et al. 2022

Antioxidants

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Chemotherapy has been a standard intervention for a variety of cancers to impede tumor growth, mainly by inducing apoptosis. However, development of resistance to this regimen has led to a growing interest and demand for drugs targeting alternative cell death modes, such as paraptosis. Here, we designed and synthesized a novel derivative of a pyrazolo[3,4-h]quinoline scaffold (YRL1091), evaluated its cytotoxic effect, and elucidated the underlying molecular mechanisms of cell death in MDA-MB-231 and MCF-7 breast cancer (BC) cells. We found that YRL1091 induced cytotoxicity in these cells with numerous cytoplasmic vacuoles, one of the distinct characteristics of paraptosis. YRL1091-treated BC cells displayed several other distinguishing features of paraptosis, excluding autophagy or apoptosis. Briefly, YRL1091-induced cell death was associated with upregulation of microtubule-associated protein 1 light chain 3B, downregulation of multifunctional adapter protein Alix, and activation of extracellular signal-regulated kinase 1/2 and c-Jun N-terminal kinase. Furthermore, the production of reactive oxygen species (ROS) and newly synthesized proteins were also observed, subsequently causing ubiquitinated protein accumulation and endoplasmic reticulum (ER) stress. Collectively, these results indicate that YRL1091 induces paraptosis in BC cells through ROS generation and ER stress. Therefore, YRL1091 can serve as a potential candidate for the development of a novel anticancer drug triggering paraptosis, which may provide benefit for the treatment of cancers resistant to conventional chemotherapy.

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Paraptosis

Cited by 6 publications

References 45 publications

Multifunctional Heterometallic Ir^III−Au^I Probes as Promising Anticancer and Antiangiogenic Agents

Multifunctional Heterometallic Ir^III−Au^I Probes as Promising Anticancer and Antiangiogenic Agents

Transcriptomic Analysis of the Anticancer Effects of Annatto Tocotrienol, Delta-Tocotrienol and Gamma-Tocotrienol on Chondrosarcoma Cells

Induction of Paraptotic Cell Death in Breast Cancer Cells by a Novel Pyrazolo[3,4-h]quinoline Derivative through ROS Production and Endoplasmic Reticulum Stress

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Paraptosis

Cited by 6 publications

References 45 publications

Multifunctional Heterometallic IrIII−AuI Probes as Promising Anticancer and Antiangiogenic Agents

Multifunctional Heterometallic IrIII−AuI Probes as Promising Anticancer and Antiangiogenic Agents

Transcriptomic Analysis of the Anticancer Effects of Annatto Tocotrienol, Delta-Tocotrienol and Gamma-Tocotrienol on Chondrosarcoma Cells

Induction of Paraptotic Cell Death in Breast Cancer Cells by a Novel Pyrazolo[3,4-h]quinoline Derivative through ROS Production and Endoplasmic Reticulum Stress

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Product

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Multifunctional Heterometallic Ir^III−Au^I Probes as Promising Anticancer and Antiangiogenic Agents

Multifunctional Heterometallic Ir^III−Au^I Probes as Promising Anticancer and Antiangiogenic Agents