Diethyldithiocarbamate-ferrous oxide nanoparticles inhibit human and mouse glioblastoma stemness: aldehyde dehydrogenase 1A1 suppression and ferroptosis induction

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: April 24, 2024

The development of effective therapy for eradicating glioblastoma stem cells remains a major challenge due to their aggressive growth, chemoresistance and radioresistance which are mainly conferred by aldehyde dehydrogenase (ALDH)1A1. latter is the main stemness mediator via enhancing signaling pathways Wnt/β-catenin, phosphatidylinositol 3-kinase/AKT, hypoxia. Furthermore, ALDH1A1 mediates therapeutic resistance inactivating drugs, stimulating expression drug efflux transporters, detoxifying reactive radical species, thereby apoptosis arresting. Recent reports disclosed potent broad-spectrum anticancer activities unique nanocomplexes diethyldithiocarbamate (DE, inhibitor) with ferrous oxide nanoparticles (FeO NPs) inducing lipid peroxidation-dependent non-apoptotic (iron accumulation-triggered ferroptosis), was reported. Accordingly, anti-stemness activity (DE-FeO investigated against human mouse glioma (GSCs) radioresistant GSCs (GSCs-RR). DE-FeO NPs exhibited strongest growth inhibition effect on treated (MGG18 JX39P), (GS PDGF-GSC) (IC 50 ≤ 70 161 μg/mL, respectively). also revealed higher inhibitory impact than standard chemotherapy (temozolomide, TMZ) self-renewal, cancer repopulation, chemoresistance, potentials. Besides, surpassed TMZ regarding relative all studied genes, as well p-AKT/AKT ratio in MGG18, GS (MGG18-RR GS-RR). This influence primarily attributed ferroptosis induction, confirmed significant elevation cellular oxygen species peroxidation depletion glutathione peroxidase 4. recorded optimal Log P value crossing blood brain barrier. vitro novel study declared potency collapsing GSCs-RR improving sensitivity radiotherapy, indicating that may be promising remedy GBM. Glioma animal models will needed in-depth studies its safe effectiveness.

Language: Английский

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Superior cuproptotic efficacy of diethyldithiocarbamate-Cu4O3 nanoparticles over diethyldithiocarbamate-Cu2O nanoparticles in metastatic hepatocellular carcinoma

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: July 15, 2024

Metastatic hepatocellular carcinoma (HC) is a serious health concern. The stemness of cancer stem cells (CSCs) key driver for HC tumorigenesis, apoptotic resistance, and metastasis, functional mitochondria are critical its maintenance. Cuproptosis Cu-dependent non-apoptotic pathway (mitochondrial dysfunction) via inactivating mitochondrial enzymes (pyruvate dehydrogenase "PDH" succinate "SDH"). To effectively treat metastatic HC, it necessary to induce selective cuproptosis (for halting genes) with oxidative imbalance increasing cell susceptibility inducing non-CSCs death). Herein, two types Cu oxide nanoparticles (Cu

Language: Английский

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Advances in non-apoptotic regulated cell death: implications for malignant tumor treatment

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 30, 2025

Cell death mechanisms are broadly classified into accidental cell (ACD) and regulated (RCD). ACD such as necrosis, is an uncontrolled, process, while RCD tightly by specific signaling pathways molecular mechanisms. Tumor cells characterized their ability to evade sustain uncontrolled proliferation. The failure of programmed a key contributor tumor initiation, progression, resistance cancer therapies. Traditionally, research has focused primarily on apoptosis the dominant form in cancer. However, emerging evidence highlights importance other non-apoptotic forms RCD, pyroptosis, ferroptosis, necroptosis, parthanatos, tumorigenesis treatment response. These gaining attention for potential roles overcoming therapy resistance. In this review, we will discuss recent advances study malignant tumors explore therapeutic implications, offering insights new targets strategies.

Language: Английский

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Ferroptosis- and stemness inhibition-mediated therapeutic potency of ferrous oxide nanoparticles-diethyldithiocarbamate using a co-spheroid 3D model of pancreatic cancer

Journal of Gastroenterology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 31, 2025

Language: Английский

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Diethyldithiocarbamate-copper complex ignites the tumor microenvironment through NKG2D-NKG2DL axis

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 12, 2025

Advanced metastatic colorectal cancer (CRC) with deficient DNA mismatch repair (MMR-d), or immune-hot CRCs, show significantly improved clinical outcomes compared to MMR-proficient (MMR-p), immune-cold CRCs. While the prior represents about 5% of all latter represent 95% and are characterized by low immunogenicity. This study investigates bis-diethyldithiocarbamate (CuET), a novel anticancer compound, its impact on tumor microenvironment (TME). CuET is shown convert immunologically inactive tumors into hotbeds antitumor immune responses, marked increased lymphocyte infiltration, heightened cytotoxicity natural killer (NK) T cells, enhanced non-self recognition lymphocytes. The potent in vivo safety efficacy established. In summary, transforms TME, bolstering NK cell refining through non-classical activation via NKG2D/NKG2DL axis. unveils mechanism action for CuET: immunomodulator capable turning cold hot.

Language: Английский

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Cancer Stem Cells: Robust Features and Therapeutic Targets

Interdisciplinary cancer research, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

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