Ultrastructural Analysis of Cancer Cells Treated with the Radiopharmaceutical Radium Dichloride ([223Ra]RaCl2): Understanding the Effect on Cell Structure

Filho, Joel Félix Silva Diniz; Barros, Aline Oliveira da Silva de; Pijeira, Martha Sahylí Ortega; Ricci, Esther Lopes; Midlej, Victor; Baroni, Mariana Pelissari Monteiro Aguiar; Santos, Clenilton Costa dos; Alencar, Luciana Magalhães Rebêlo; Santos-Oliveira, Ralph

doi:10.3390/cells12030451

Cited by 3 publications

(3 citation statements)

References 41 publications

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“…[43,44] Other results suggest that alpha-emitter 223 Ra destroys cell membrane and induces cellular autophagy. [45] Both indirect and direct effects induced by alpha-emitter radiation contribute to the activation of several pathways that leads toward damage repair systems, senescence or cell death, through mechanisms such as apoptosis, autophagy, necrosis, and mitotic catastrophe. [46,47] Many studies also report other cell death modalities following IR, such as necroptosis, ferroptosis, and pyroptosis which have a distinct outcome on the immune system.…”

Section: Discussionmentioning

confidence: 99%

Alpha‐Emitter Radium‐223 Induces STING‐Dependent Pyroptosis to Trigger Robust Antitumor Immunity

Yang,

Liu,

Lou

et al. 2023

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Radium‐223 (223Ra) is the first‐in‐class alpha‐emitter to mediate tumor eradication, which is commonly thought to kill tumor cells by directly cleaving double‐strand DNA. However, the immunogenic characteristics and cell death modalities triggered by 223Ra remain unclear. Here, it is reported that the 223Ra irradiation induces the pro‐inflammatory damage‐associated molecular patterns including calreticulin, HMGB1, and HSP70, hallmarks of tumor immunogenicity. Moreover, therapeutic 223Ra retards tumor progression by triggering pyroptosis, an immunogenic cell death. Mechanically, 223Ra‐induced DNA damage leads to the activation of stimulator of interferon genes (STING)‐mediated DNA sensing pathway, which is critical for NLRP3 inflammasome‐dependent pyroptosis and subsequent DCs maturation as well as T cell activation. These findings establish an essential role of STING in mediating alpha‐emitter 223Ra‐induced antitumor immunity, which provides the basis for the development of novel cancer therapeutic strategies and combinatory therapy.

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Section: Discussionmentioning

confidence: 99%

Alpha‐Emitter Radium‐223 Induces STING‐Dependent Pyroptosis to Trigger Robust Antitumor Immunity

Yang,

Liu,

Lou

et al. 2023

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“…The morphological and ultrastructural analyses was performed using an HT7800 RuliTEM microscope (Hitachi, JPN). 39…”

Section: Analysis Of Subcellular Mda-mb-231 Morphology Following the ...mentioning

confidence: 99%

Tarin-Loaded Nanoliposomes Activate Apoptosis and Autophagy and Inhibit the Migration of Human Mammary Adenocarcinoma Cells

Cardoso,

Pereira,

Freitas

et al. 2023

IJN

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Background: Tarin, a lectin purified from Colocasia esculenta, promotes in vitro and in vivo immunomodulatory effects allied to promising anticancer and antimetastatic effects against human adenocarcinoma mammary cells. This makes this 47 kDa-protein a natural candidate against human breast cancer, a leading cause of death among women. Tarin encapsulated in pegylated nanoliposomes displays increased effectiveness in controlling the proliferation of a mammary adenocarcinoma lineage comprising MDA-MB-231 cells. Methods: The mechanisms enrolled in anticancer and antimetastatic responses were investigated by treating MDA-MB-231 cells with nano-encapsulated tarin at 72 μg/mL for up to 48h through flow cytometry and transmission electron microscopy (TEM). The safety of nano-encapsulated tarin towards healthy tissue was also assessed by the resazurin viability assay, and the effect of nanoencapsulated tarin on cell migration was evaluated by scratch assays. Results: Ultrastructural analyses of MDA-MB-231 cells exposed to nanoencapsulated tarin revealed the accumulation of autophagosomes and damaged organelles, compatible with autophagy-dependent cell death. On the other hand, the flow cytometry investigation detected the increased occurrence of acidic vacuolar organelles, a late autophagosome trait, along with the enhanced presence of apoptotic cells, activated caspase-3/7, and cell cycle arrest at G0/G1. No deleterious effects were observed in healthy fibroblast cells following tarin nanoencapsulated exposition, in contrast to reduced viability in cells exposed to free tarin. The migration of MDA-MB -231 cells was inhibited by nano-encapsulated tarin, with delayed movement by 24 h compared to free tarin. Conclusion:The nanoliposome formulation delivers tarin in a delayed and sustained manner, as evidenced by the belated and potent antitumoral and anti-migration effects on adenocarcinoma cells, with no toxicity to healthy cells. Although further investigations are required to fully understand antitumorigenic tarin mechanisms, the activation of both apoptotic and autophagic machineries along with the caspase-3/7 pathway, and cell cycle arrest may comprise a part of these mechanisms.

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“…Tissue shape and mechanics, for example, are critical for regulating organ function. AFM can capture high-resolution images and connect them with mechanical and viscoelastic properties, making it an ideal tool for studying blood cells, cancer cells, , and viral particles, among other biological systems . It is worth noting that AFM can be utilized in the physiological circumstances of cells or biomolecules.…”

Section: Introductionmentioning

confidence: 99%

Atomic Force Microscopy Applied to the Study of Tauopathies

do Nascimento Amorim,

Silva França,

Santos-Oliveira

et al. 2024

ACS Chem. Neurosci.

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Atomic force microscopy (AFM) is a scanning probe microscopy technique which has a physical principle, the measurement of interatomic forces between a very thin tip and the surface of a sample, allowing the obtaining of quantitative data at the nanoscale, contributing to the surface study and mechanical characterization. Due to its great versatility, AFM has been used to investigate the structural and nanomechanical properties of several inorganic and biological materials, including neurons affected by tauopathies. Tauopathies are neurodegenerative diseases featured by aggregation of phosphorylated tau protein inside neurons, leading to functional loss and progressive neurotoxicity. In the broad universe of neurodegenerative diseases, tauopathies comprise the most prevalent, with Alzheimer's disease as its main representative. This review highlights the use of AFM as a suitable research technique for the study of cellular damages in tauopathies, even in early stages, allowing elucidation of pathogenic mechanisms of these diseases.

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Ultrastructural Analysis of Cancer Cells Treated with the Radiopharmaceutical Radium Dichloride ([223Ra]RaCl2): Understanding the Effect on Cell Structure

Cited by 3 publications

References 41 publications

Alpha‐Emitter Radium‐223 Induces STING‐Dependent Pyroptosis to Trigger Robust Antitumor Immunity

Alpha‐Emitter Radium‐223 Induces STING‐Dependent Pyroptosis to Trigger Robust Antitumor Immunity

Tarin-Loaded Nanoliposomes Activate Apoptosis and Autophagy and Inhibit the Migration of Human Mammary Adenocarcinoma Cells

Atomic Force Microscopy Applied to the Study of Tauopathies

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