Progress in the discovery and development of small molecule methuosis inducers

Ye, Tao; Shan, Peipei; Zhang, Hua

doi:10.1039/d3md00155e

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2024

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Cited by 3 publications

References 81 publications

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Navigating the complexities of cell death: Insights into accidental and programmed cell death

Lotfi,

Rassouli

2024

Tissue and Cell

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Navigating the complexities of cell death: Insights into accidental and programmed cell death

Lotfi,

Rassouli

2024

Tissue and Cell

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Cytoskeleton disruption and plasma membrane damage determine methuosis of normal and malignant cells

Gao,

Dong,

Xiao

et al. 2024

Preprint

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Methuosis represents a novel cell death modality characterized by catastrophic cytoplasmic vacuolization in normal and malignant cells. However, the critical role and the underlying mechanism of cytoskeleton and plasma membrane damage in methuotic cells are largely unknown. Herein, maduramicin-treated myocardial cells (H9c2) and indole chalcone-exposed glioma cells (U251) were used as methuosis model to uncover this secret. We found that cytoskeleton protein F-actin, α-tubulin, β-tubulin and filamin A/B were disrupted in a reversible-dependent manner. In addition, RhoA-ROCK1 signaling pathway mediated cytoskeleton disruption in methuotic cells. Excessive cytoplasmic vacuolization triggered cellular plasma membrane damage and the release of DAMPs, including LDH, ATP and CRT. Furthermore, at the end phase of methuotic cells, plasma membrane was damaged independent of pore-forming protein p-MLKL and GSDMD. Endosomal sorting complex required for transport (ESCRT)-Ⅲ especially its subunit CHMP3 and CHMP5 negatively regulated excessive vacuolization-induced plasma membrane damage in cells undergoing methuosis. In conclusion, for the first time, the critical role and potential mechanism of cytoskeleton and plasma membrane damage in methuotic cells are known, which would facilitate the employment of methuosis in life science and pharmacology.

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Methuosis, Alkaliptosis, and Oxeiptosis and Their Significance in Anticancer Therapy

Bartoszewska,

Florek,

Zagórski

et al. 2024

Cells

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Understanding morphological, biochemical, and functional aspects of cell death is essential for targeting new cancer therapies. Even though many different mechanisms of cell death are identified, it is crucial to highlight the role of new and lesser-known pathways, including methuosis, alkaliptosis, and oxeiptosis. The aim of this review was to summarize the data about cell death mechanisms—methuosis, alkaliptosis, and oxeiptosis—and their role in cancer treatment. Unique molecular mechanisms and cellular outcomes characterize each of these forms of cell death. This research on methuosis, alkaliptosis, and oxeiptosis provides a better understating of cell death biology and creates novel opportunities for neoplasm management.

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Progress in the discovery and development of small molecule methuosis inducers

Abstract: Current cancer chemotherapies rely mainly on the induction of apoptosis of tumor cells, while drug resistance arising from conventional chemicals has always been a big challenge. In recent years, more...

Cited by 3 publications

References 81 publications

Navigating the complexities of cell death: Insights into accidental and programmed cell death

Navigating the complexities of cell death: Insights into accidental and programmed cell death

Cytoskeleton disruption and plasma membrane damage determine methuosis of normal and malignant cells

Methuosis, Alkaliptosis, and Oxeiptosis and Their Significance in Anticancer Therapy

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