Can inflammasomes promote the pathophysiology of glioblastoma multiforme? A view about the potential of the anti-inflammasome therapy as pharmacological target

Rolim, Giovanna Barros; Lima, Ayara Jhulia Palmeira Dantas; Cardoso, Vitória Ingryd Dos Santos; Soares, Érika de Fátima Machado; Nunes, Danielle Nascimento; Barros, Herbert Charles Silva; Leite, Anderson Brandão; Alexandre-Moreira, Magna Suzana; Duarte, Alysson Wagner Fernandes; Marques, Carolinne de Sales; Fraga, Carlos Alberto de Carvalho; Queiroz, Aline Cavalcanti de

doi:10.1016/j.critrevonc.2022.103641

Cited by 9 publications

(6 citation statements)

References 51 publications

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“…It has been found that pain from a growing tumor, swallowing problems from radiation therapy, nausea, loss of appetite, or mouth ulcers, sometimes caused by chemotherapy, can lead to involuntary weight loss, which is one of the serious side effects of cancer and its treatment for many patients 66 . Hence, in order to assess the treatment side effects, animal weight (among surviving mice) was monitored throughout the study.…”

Section: Discussionmentioning

confidence: 99%

Comparative assessment of direct and indirect cold atmospheric plasma effects, based on helium and argon, on human glioblastoma: an in vitro and in vivo study

Bakhtiyari-Ramezani,

Nohekhan,

Akbari

et al. 2024

Sci Rep

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Recent research has highlighted the promising potential of cold atmospheric plasma (CAP) in cancer therapy. However, variations in study outcomes are attributed to differences in CAP devices and plasma parameters, which lead to diverse compositions of plasma products, including electrons, charged particles, reactive species, UV light, and heat. This study aimed to evaluate and compare the optimal exposure time, duration, and direction-dependent cellular effects of two CAPs, based on argon and helium gases, on glioblastoma U-87 MG cancer cells and an animal model of GBM. Two plasma jets were used as low-temperature plasma sources in which helium or argon gas was ionized by high voltage (4.5 kV) and frequency (20 kHz). In vitro assessments on human GBM and normal astrocyte cell lines, using MTT assays, flow cytometry analysis, wound healing assays, and immunocytochemistry for Caspase3 and P53 proteins, demonstrated that all studied plasma jets, especially indirect argon CAP, selectively induced apoptosis, hindered tumor cell growth, and inhibited migration. These effects occurred concurrently with increased intracellular levels of reactive oxygen species and decreased total antioxidant capacity in the cells. In vivo results further supported these findings, indicating that single indirect argon and direct helium CAP therapy, equal to high dose Temozolomide treatment, induced tumor cell death in a rat model of GBM. This was concurrent with a reduction in tumor size observed through PET-CT scan imaging and a significant increase in the survival rate. Additionally, there was a decrease in GFAP protein levels, a significant GBM tumor marker, and an increase in P53 protein expression based on immunohistochemical analyses. Furthermore, Ledge beam test analysis revealed general motor function improvement after indirect argon CAP therapy, similar to Temozolomide treatment. Taken together, these results suggest that CAP therapy, using indirect argon and direct helium jets, holds great promise for clinical applications in GBM treatment.

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Section: Discussionmentioning

confidence: 99%

Comparative assessment of direct and indirect cold atmospheric plasma effects, based on helium and argon, on human glioblastoma: an in vitro and in vivo study

Bakhtiyari-Ramezani,

Nohekhan,

Akbari

et al. 2024

Sci Rep

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“…Particularly, high-grade glioma-associated microglia were observed to secrete IL-1β via the NLRP1 inflammasome, promoting tumor progression [ 28 ]. In addition, in glioma cells, overexpression of NLRP12 and NLRC4 inflammasome-associated genes and proteins contributed to malignancy and poor prognosis [ 42 ]. In a lung brain metastasis xenograft model, Nlrp3 and Il1b transcripts were upregulated in tumor-associated macrophages, suggesting possible inflammasome activation [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Inflammasome activation in peritumoral astrocytes is a key player in breast cancer brain metastasis development

Mészáros,

Molnár,

Fazakas

et al. 2023

acta neuropathol commun

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Inflammasomes, primarily responsible for the activation of IL-1β, have emerged as critical regulators of the tumor microenvironment. By using in vivo and in vitro brain metastasis models, as well as human samples to study the role of the NLRP3 inflammasome in triple-negative breast cancer (TNBC) brain metastases, we found NLRP3 inflammasome components and IL-1β to be highly and specifically expressed in peritumoral astrocytes. Soluble factors from TNBC cells induced upregulation and activation of NLRP3 and IL-1β in astrocytes, while astrocyte-derived mediators augmented the proliferation of metastatic cells. In addition, inhibition of NLRP3 inflammasome activity using MCC950 or dampening the downstream effect of IL-1β prevented the proliferation increase in cancer cells. In vivo, MCC950 reduced IL-1β expression in peritumoral astrocytes, as well as the levels of inflammasome components and active IL-1β. Most importantly, significantly retarded growth of brain metastatic tumors was observed in mice treated with MCC950. Overall, astrocytes contribute to TNBC progression in the brain through activation of the NLRP3 inflammasome and consequent IL-1β release. We conclude that pharmacological targeting of inflammasomes may become a novel strategy in controlling brain metastatic diseases.

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“…IL-1β upregulated cyclooxygenase-2 that encoded prostaglandins then mediate MDSC propagation [64]. IL-1β also activated STAT3 in glioma cells, which decreased the population of DC and increased the population of MDSC [65].…”

Section: Il-1βmentioning

confidence: 99%

The role of pyroptosis in modulating the tumor immune microenvironment

Wang

2022

Biomark Res

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The tumor immune microenvironment (TIME) plays a key role in immunosuppression in cancer, which results in tumorigenesis and tumor progression, and contributes to insensitivity to chemotherapy and immunotherapy. Understanding the mechanism of TIME formation is critical for overcoming cancer. Pyroptosis exerts a dual role in modulating the TIME. In this review, we summarize the regulatory mechanisms of pyroptosis in modulating the TIME and the potential application of targeted pyroptosis therapy in the clinic. Several treatments targeting pyroptosis have been developed; however, the majority of treatments are still in preclinical studies. Only a few agents have been used in clinic, but the outcomes are unsatisfactory. More studies are necessary to determine the role of pyroptosis in cancer, and more research is required to realize the application of treatments targeting pyroptosis in the clinic.

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Can inflammasomes promote the pathophysiology of glioblastoma multiforme? A view about the potential of the anti-inflammasome therapy as pharmacological target

Cited by 9 publications

References 51 publications

Comparative assessment of direct and indirect cold atmospheric plasma effects, based on helium and argon, on human glioblastoma: an in vitro and in vivo study

Comparative assessment of direct and indirect cold atmospheric plasma effects, based on helium and argon, on human glioblastoma: an in vitro and in vivo study

Inflammasome activation in peritumoral astrocytes is a key player in breast cancer brain metastasis development

The role of pyroptosis in modulating the tumor immune microenvironment

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