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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Oxidative cell death in cancer: mechanisms and therapeutic opportunities

Cell Death and Disease, Год журнала: 2024, Номер 15(8)

Опубликована: Авг. 1, 2024

Abstract Reactive oxygen species (ROS) are highly reactive oxygen-containing molecules generated as natural byproducts during cellular processes, including metabolism. Under normal conditions, ROS play crucial roles in diverse functions, cell signaling and immune responses. However, a disturbance the balance between production antioxidant defenses can lead to an excessive buildup, causing oxidative stress. This stress damages essential components, lipids, proteins, DNA, potentially culminating death. form of death take various forms, such ferroptosis, apoptosis, necroptosis, pyroptosis, paraptosis, parthanatos, oxeiptosis, each displaying distinct genetic, biochemical, characteristics. The investigation holds promise for development pharmacological agents that used prevent tumorigenesis or treat established cancer. Specifically, targeting key SLC7A11, GCLC, GPX4, TXN, TXNRD, represents emerging approach inducing cancer cells. review provides comprehensive summary recent progress, opportunities, challenges therapy.

Язык: Английский

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Paraptosis: a non-classical paradigm of cell death for cancer therapy

Acta Pharmacologica Sinica, Год журнала: 2023, Номер 45(2), С. 223 - 237

Опубликована: Сен. 15, 2023

Язык: Английский

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Molecular mechanisms and clinical implications of the gold drug auranofin

Coordination Chemistry Reviews, Год журнала: 2023, Номер 493, С. 215323 - 215323

Опубликована: Июль 9, 2023

Язык: Английский

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Targeting paraptosis in cancer: opportunities and challenges

Cancer Gene Therapy, Год журнала: 2024, Номер 31(3), С. 349 - 363

Опубликована: Янв. 4, 2024

Язык: Английский

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Auranofin-Loaded Chitosan Nanoparticles Demonstrate Potency against Triple-Negative Breast Cancer

ACS Applied Bio Materials, Год журнала: 2024, Номер 7(3), С. 2012 - 2022

Опубликована: Март 7, 2024

Triple-negative breast cancer (TNBC) remains a clinical challenge due to molecular, metabolic, and genetic heterogeneity as well the lack of validated drug targets. Thus, therapies or delivery paradigms are needed. Gold-derived compounds including FDA-approved drug, auranofin have shown promise effective anticancer agents against several tumors. To improve solubility bioavailability auranofin, we hypothesized that nanodelivery using biodegradable chitosan modified polyethylene glycol (PEG) nanoparticles (NPs) will enhance activity TNBC by comparing best nanoformulation with free drug. The selection was based on synthesis various PEG copolymers via formaldehyde-mediated engraftment onto form [chitosan-g-PEG] copolymer. Furthermore, altered physiochemical properties copolymer formaldehyde ratio towards (CP 1–4 NPs). Following recruitment polymer surface, explored how this process influenced stiffness nanoparticle atomic force microscopy (AFM), factor crucial for in vitro vivo studies. Our objective ensure full functionality inherent parent maintained without allowing overshadow chitosan's unique cationic while improving neutral pH. Hence, CP 2 NP chosen. demonstrate efficacy good carrier administered dose 3 mg/kg contrast which given at 5 mg/kg. In studies revealed potency encapsulated cells severe necrotic effect following treatment superior auranofin. conclusion, chitosan-g-PEG potential be an excellent system increasing its effectiveness potentially reducing limitations.

Язык: Английский

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Antioxidant Enzymes and Their Potential Use in Breast Cancer Treatment

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(11), С. 5675 - 5675

Опубликована: Май 23, 2024

According to the World Health Organization (WHO), breast cancer (BC) is deadliest and most common type of worldwide in women. Several factors associated with BC exert their effects by modulating state stress. They can induce genetic mutations or alterations cell growth, encouraging neoplastic development production reactive oxygen species (ROS). ROS are able activate many signal transduction pathways, producing an inflammatory environment that leads suppression programmed death promotion tumor proliferation, angiogenesis, metastasis; these promote progression malignant neoplasms. However, cells have both non-enzymatic enzymatic antioxidant systems protect them neutralizing harmful ROS. In this sense, enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reductase (GR), thioredoxin (TrxR), peroxiredoxin (Prx) body from diseases caused oxidative damage. review, we will discuss mechanisms through which some antioxidants inhibit carcinogenesis, well new therapeutic proposals developed complement traditional treatments.

Язык: Английский

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Integrated Bioinformatic Analyses Reveal Thioredoxin as a Putative Marker of Cancer Stem Cells and Prognosis in Prostate Cancer

Cancer Informatics, Год журнала: 2025, Номер 24

Опубликована: Янв. 1, 2025

Objectives: Prostate cancer stem cells (CSCs) play an important role in cell survival, proliferation, metastasis, and recurrence; thus, removing CSCs is for complete removal. However, the mechanisms underlying CSC functions remain largely unknown, making it difficult to develop new anticancer drugs targeting CSCs. Herein, we aimed identify novel factors that regulate stemness predict prognosis. Methods: We reanalyzed 2 single-cell RNA sequencing data of prostate (PCa) tissues using Seurat. used gene set enrichment analysis (GSEA) estimate identified common upregulated genes between these datasets. To investigate whether its expression levels change over differentiation, performed a trajectory monocle 3. In addition, GSEA helped us understand how stemness. Finally, assess their clinical significance, Cancer Genome Atlas database evaluate impact on Results: The thioredoxin ( TXN), redox enzyme, was approximately 1.2 times higher than PCa P < 1 × 10 −10 ), TXN decreased differentiation. suggested intracellular signaling pathways, including MYC, may be involved regulation by TXN. Furthermore, correlated with poor prognosis (P .05) patients high Conclusions: Despite limited sample size our study need further vitro vivo experiments demonstrate functionally regulates CSCs, findings suggest serve as therapeutic target against Moreover, could useful marker predicting patients.

Язык: Английский

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Integrating Machine Learning and Bulk and Single-Cell RNA Sequencing to Decipher Diverse Cell Death Patterns for Predicting the Prognosis of Neoadjuvant Chemotherapy in Breast Cancer

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(8), С. 3682 - 3682

Опубликована: Апрель 13, 2025

Breast cancer (BRCA) continues to pose a serious risk women’s health worldwide. Neoadjuvant chemotherapy (NAC) is critical treatment strategy. Nevertheless, the heterogeneity in outcomes necessitates identification of reliable biomarkers and prognostic models. Programmed cell death (PCD) pathways serve as factor tumor development response. However, relationship between diverse patterns PCD NAC BRCA remains unclear. We integrated machine learning multiple bioinformatics tools explore association 19 prognosis within cohort 921 patients treated with from seven multicenter cohorts. A model based on PCD-related genes (PRGs) was constructed evaluated using combination 117 algorithms. Immune infiltration analysis, mutation pharmacological single-cell RNA sequencing (scRNA-seq) were conducted genomic profile clinical significance these BRCA. Immunohistochemistry (IHC) employed validate expression select (UGCG, BTG22, TNFRSF21, MYB) tissues. PRGs by signature comprising 20 DEGs forecast patients. The demonstrated excellent predictive accuracy, high concordance index (C-index) 0.772, validated across independent datasets. Our results strong developed survival prognosis, pathological features, immune infiltration, microenvironment (TME), gene mutations, drug sensitivity for Moreover, IHC studies further that certain tissues significantly associated efficacy emerged an autonomous predictor influencing outcome are first integrate bulk scRNA-seq decode various mechanisms unique model, PRGs, provides novel comprehensive strategy predicting This not only aids understanding underlying but also offers insights into personalized strategies, potentially improving patient outcomes.

Язык: Английский

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Auranofin Induces Lethality Driven by Reactive Oxygen Species in High-Grade Serous Ovarian Cancer Cells

Cancers, Год журнала: 2023, Номер 15(21), С. 5136 - 5136

Опубликована: Окт. 25, 2023

High-grade serous ovarian cancer (HGSOC) accounts for 70% of cases, and the survival rate remains remarkably low due to lack effective long-term consolidation therapies. Clinical remission can be temporarily induced by platinum-based chemotherapy, but death subsequently results from extensive growth a platinum-resistant component tumor. This work explores novel treatment against HGSOC using gold complex auranofin (AF). AF primarily functions as pro-oxidant inhibiting thioredoxin reductase (TrxR), an antioxidant enzyme overexpressed in cancer. We investigated effect on TrxR activity various mechanisms cytotoxicity cells that are clinically sensitive or resistant platinum. In addition, we studied interaction between another pro-oxidant, L-buthionine sulfoximine (L-BSO), anti-glutathione (GSH) compound. demonstrated potently inhibited reduced vitality viability regardless their sensitivities showed induces accumulation reactive oxygen species (ROS), triggers depolarization mitochondrial membrane, kills inducing apoptosis. Notably, AF-induced cell was abrogated ROS-scavenger N-acetyl cysteine (NAC). lethality associated with activation caspases-3/7 generation DNA damage, effects were also prevented presence NAC. Finally, when L-BSO combined, observed synergistic cells, which mediated further increase ROS decrease levels GSH. summary, our support concept used alone combination kill sensitivity platinum, suggesting depletion antioxidants is efficient strategy mitigate course this disease.

Язык: Английский

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