Paraptosis: a unique cell death mode for targeting cancer

Frontiers in Pharmacology, Год журнала: 2023, Номер 14

Опубликована: Июнь 15, 2023

Programmed cell death (PCD) is the universal process that maintains cellular homeostasis and regulates all living systems' development, health disease. Out of all, apoptosis one major PCDs was found to play a crucial role in many disease conditions, including cancer. The cancer cells acquire ability escape apoptotic death, thereby increasing their resistance towards current therapies. This issue has led need search for alternate forms programmed mechanisms. Paraptosis an alternative pathway characterized by vacuolation damage endoplasmic reticulum mitochondria. Many natural compounds metallic complexes have been reported induce paraptosis lines. Since morphological biochemical features are much different from other PCDs, it understand modulators governing it. In this review, we highlighted factors trigger specific mediating pathway. Recent findings include inducing anti-tumour T-cell immunity immunogenic responses against A significant played also scaled its importance knowing mechanism. study xenograft mice, zebrafish model, 3D cultures, novel paraptosis-based prognostic model low-grade glioma patients broad aspect potential involvement field therapy. co-occurrence modes with photodynamic therapy combinatorial treatments tumour microenvironment summarized here. Finally, growth, challenges, future perspectives research discussed review. Understanding unique PCD would help develop combat chemo-resistance various

Язык: Английский

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A Microenvironment Dual‐Responsive Nano‐Drug Equipped with PD‐L1 Blocking Peptide Triggers Immunogenic Pyroptosis for Prostate Cancer Self‐Synergistic Immunotherapy

Advanced Functional Materials, Год журнала: 2023, Номер 33(16)

Опубликована: Янв. 25, 2023

Abstract Induction of immunogenic cell death (ICD) in tumor combined with immune checkpoint blockade (ICB) therapy is widely developed to improve the efficacy cancer immunotherapy. However, current ICD induced based on apoptosis, i.e., often restricted immunogenicity owing inflammatory quenching that occurs early apoptosis. Recently, pyroptosis demonstrated be a more efficient form, pyroptosis. The contents released during can powerfully activate immunogenicity. Herein, first, it lower doses epigenetic drug decitabine increase GSDME expression prostate (PCa) RM‐1 cells and successfully induce an apoptosis‐pyroptosis transition after photodynamic (PDT). Subsequently, microenvironment dual‐responsive nano‐drug equipped PD‐L1 blocking peptide (TSD@LSN‐D) for self‐synergistic poorly PCa model confirm powerful antitumor response evoked by TSD@LSN‐D not only effectively inhibit primary but also form long‐term memory prevent recurrence metastasis. To best authors’ knowledge, this work presents first concept promotes apoptosis–pyroptosis PDT through modulation. Furthermore, combination ICB opens new platform

Язык: Английский

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Lactobacillus rhamnosus GG triggers intestinal epithelium injury in zebrafish revealing host dependent beneficial effects

iMeta, Год журнала: 2024, Номер 3(2)

Опубликована: Март 25, 2024

Abstract Lactobacillus rhamnosus GG (LGG), the well‐characterized human‐derived probiotic strain, possesses excellent properties in maintenance of intestinal homeostasis, immunoregulation and defense against gastrointestinal pathogens mammals. Here, we demonstrate that SpaC pilin LGG causes epithelium injury by inducing cell pyroptosis gut microbial dysbiosis zebrafish. Dietary activates Caspase‐3−GSDMEa pathways epithelium, promotes increases lipopolysaccharide (LPS)‐producing microbes The increased LPS subsequently Gaspy2−GSDMEb pathway. Further analysis reveals is initiated species‐specific recognition TLR4ba, which accounts for species‐specificity SpaC‐inducing observed pyroptosis‐driven zebrafish suggest host‐specific beneficial/harmful mechanisms are critical safety issues when applying probiotics derived from other host species need more attention.

Язык: Английский

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Hippocampal HDAC6 promotes POCD by regulating NLRP3-induced microglia pyroptosis via HSP90/HSP70 in aged mice

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Год журнала: 2024, Номер 1870(5), С. 167137 - 167137

Опубликована: Март 24, 2024

Postoperative Cognitive Dysfunction (POCD) has attracted increased attention, but its precise mechanism remains to be explored. This study aimed figure out whether HDAC6 could regulate NLRP3-induced pyroptosis by modulating the functions of HSP70 and HSP90 in microglia participate postoperative cognitive dysfunction aged mice. Animal models mice were established splenectomy under sevoflurane anesthesia. Morris water maze was used examine function motor ability. Sixteen-months-old C57BL/6 male randomly divided into six groups: control group (C group), sham surgery (SA (S + inhibitor ACY-1215 (ACY Apoptozole (AP solvent (SC group). The serum hippocampus taken after executed. protein levels HDAC6, HSP90, HSP70, NLRP3, GSDMD-N, cleaved-Caspase-1 (P20), IL-1β detected western blotting. Serum IL-1β, IL-6 S100β measured using ELISA assay, cell localization immunofluorescence. In vitro experiments, BV2 cells validate this worked microglia. P20, blotting content supernatant assay. degree acetylation interaction NLRP3 analyzed coimmunoprecipitation Splenectomy anesthesia prolong escape latency, reduce number crossing platforms, increase expression activate inflammasome induce Using activation inflammasome, spatial memory impairment. inhibit binding degradation reverse protective effect inhibitors. results acquired experiments closely resembled those vivo, LPS stimulation led release due showed anti-inflammatory exerted opposite effect. Our findings suggest that hippocampal promotes POCD regulating via HSP90/HSP70

Язык: Английский

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Simvastatin induces pyroptosis via ROS/caspase-1/GSDMD pathway in colon cancer

Cell Communication and Signaling, Год журнала: 2023, Номер 21(1)

Опубликована: Ноя. 16, 2023

Abstract Background The outcome of patients with colon cancer is still unsatisfied nowadays. Simvastatin a type statins anti-cancer activity, but its effect on cells remains unclear. present study intended to determine the underlying mechanism simvastatin in treatment cancer. Methods viability and pyroptosis rate treated untreated were analysed by CCK-8 flow cytometry assays, respectively. We used DCFH-DA detect reactive oxygen species (ROS) production. Levels markers detected western blotting analysis or immunofluorescence staining. Besides, anticancer properties further demonstrated using cell line based xenograft tumor model. Results HCT116 SW620 induced suppressed proliferation, changes expression level NLPR3, ASC, cleaved-caspase-1, mature IL-1β, IL-18 GSDMD-N. Moreover, inhibition caspase-1 ROS attenuated effects viability. In addition, it was identified that has an anti-tumor down-regulating production inducing downstream dependent subcutaneous transplantation tumors BALB/c nude mice. Conclusions Our vitro vivo results indicated through ROS/caspase-1/GSDMD pathway, thereby serving as potential agent for treatment.

Язык: Английский

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Let’s make it personal: CRISPR tools in manipulating cell death pathways for cancer treatment

Cell Biology and Toxicology, Год журнала: 2024, Номер 40(1)

Опубликована: Июль 29, 2024

Abstract Advancements in the CRISPR technology, a game-changer experimental research, have revolutionized various fields of life sciences and more profoundly, cancer research. Cell death pathways are among most deregulated cells considered as critical aspects development. Through decades, our knowledge mechanisms orchestrating programmed cellular has increased substantially, attributed to revolution cutting-edge technologies. The heroic appearance systems expanded available screening platform genome engineering toolbox detect mutations create precise edits. In that context, ability this system for identification targeting cell signaling result development therapy resistance is an auspicious choice transform accelerate individualized therapy. concept personalized stands on molecular characterization individual tumor its microenvironment order provide treatment with highest possible outcome minimum toxicity. This study explored potential technology precision by identifying specific pathways. It showed promise finding key components involved death, making it tool targeted However, also highlighted challenges limitations need be addressed future research fully realize treatment. Graphical abstract Current application through glance. A choosing appropriate biological model vitro (using established lines, animal derived cells, human stem or T cells), vivo models which can harbor tumor), ex (human/animal-derived organoids). B preparation gRNA library. C design screening, desired gRNAs phenotypic response. D CRISPR-Cas identified targets, Cas9 gene editing (Knockout, base editing, prime editing), RNA modulation (modulation splicing, interference), epigenomic edits interference/activation using dead (dCas9) (Bock et al. 2022b)

Язык: Английский

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Assessing regulated cell death modalities as an efficient tool for in vitro nanotoxicity screening: a review

Nanotoxicology, Год журнала: 2023, Номер 17(3), С. 218 - 248

Опубликована: Март 16, 2023

Nanomedicine is a fast-growing field of nanotechnology. One the major obstacles for wider use nanomaterials medical application lack standardized toxicity screening protocols assessing safety newly synthesized nanomaterials. In this review, we focus on less frequently studied nanomaterials-induced regulated cell death (RCD) modalities, including eryptosis, necroptosis, pyroptosis, and ferroptosis, as tool in vitro evaluation. We summarize latest insights into mechanisms that mediate these RCDs response to exposure. Comprehensive data from reviewed studies suggest ROS (reactive oxygen species) overproduction ROS-mediated pathways play central role activation. On other hand, also individual properties nanomaterials, size, shape, or surface charge, could determine specific with consequent RCD induction well. anticipate evaluation can become one mechanism-based methods nanotoxicology. addition assessment, necroptosis-, pyroptosis-, ferroptosis-promoting capacity simultaneously provide useful information applications be their anti-tumor potential. Moreover, detailed understanding molecular driving nanomaterials-mediated immunogenic will substantially aid novel nanodrugs development.

Язык: Английский

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Inhibition of ROS/caspase-3/GSDME-mediated pyroptosis alleviates high glucose-induced injury in AML-12 cells

Toxicology in Vitro, Год журнала: 2024, Номер 98, С. 105840 - 105840

Опубликована: Май 8, 2024

Язык: Английский

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Unlocking the potential of pyroptosis in tumor immunotherapy: a new horizon in cancer treatment

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Июнь 14, 2024

Background The interaction between pyroptosis—a form of programmed cell death—and tumor immunity represents a burgeoning field interest. Pyroptosis exhibits dual role in cancer: it can both promote development and counteract by activating immune responses that inhibit evasion encourage death. Current immunotherapy strategies, notably CAR-T therapy checkpoint inhibitors (ICIs), alongside the potential certain traditional Chinese medicinal compounds, highlight intricate relationship pyroptosis cancer immunity. As research delves deeper into mechanisms within therapy, its application enhancing emerges as novel avenue. Purpose This review aims to elucidate underlying pyroptosis, impact on biology, advancements research. Methods A comprehensive literature was conducted across PubMed, Embase, CNKI, Wanfang Database from inception study until August 22, 2023. search employed keywords such “pyroptosis”, “cancer”, “tumor”, “mechanism”, “immunity”, “gasdermin”, “ICB”, “CAR-T”, “PD-1”, “PD-L1”, “herbal medicine”, “botanical “Chinese “traditional “immunotherapy”, linked AND/OR, capture latest findings immunotherapy. Results is governed complex mechanism, with Gasdermin family playing pivotal role. While promising for application, pyroptosis’s effect still evolving. Notably, medicine ingredients have been identified inducers, meriting further exploration. Conclusion consolidates current knowledge It reveals beneficial factor immunotherapeutic landscape, suggesting leveraging developing treatment including those involving medicine, forward-looking approach oncology.

Язык: Английский

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SLC7A11 suppresses pyroptosis to alleviate rheumatoid arthritis development by modulating the IL-17 pathway

International Immunopharmacology, Год журнала: 2025, Номер 147, С. 114019 - 114019

Опубликована: Янв. 10, 2025

Язык: Английский

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