Targeting Necroptosis: A Novel Therapeutic Option for Retinal Degenerative Diseases

Zhang, Qi; Hu, Xi-Min; Zhao, Wenjuan; Ban, Xiao-Xia; Li, Yan; Huang, Yanxia; Wan, Hao; He, Ye; Liao, Lvshuang; Shang, Lei; Jiang, Bin; Qing, Guoping; Xiong, Kun

doi:10.7150/ijbs.77994

Cited by 23 publications

(12 citation statements)

References 193 publications

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“…Autophagy plays a dual role during tumor development, with an appropriate level of autophagic activity supporting cellular viability in oncological interventions and excessive activity potentially leading to cellular apoptosis [ 46 , 47 ]. In order to validate the observations derived from RNA-seq, an investigation was undertaken to explore the dose-dependent influence of PX on autophagy in TNBC cell lines.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of TNBC Cell Growth by Paroxetine: Induction of Apoptosis and Blockage of Autophagy Flux

Huang,

Wu,

et al. 2024

Cancers

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The strategy of drug repurposing has gained traction in the field of cancer therapy as a means of discovering novel therapeutic uses for established pharmaceuticals. Paroxetine (PX), a selective serotonin reuptake inhibitor typically utilized in the treatment of depression, has demonstrated promise as an agent for combating cancer. Nevertheless, the specific functions and mechanisms by which PX operates in the context of triple-negative breast cancer (TNBC) remain ambiguous. This study aimed to examine the impact of PX on TNBC cells in vitro as both a standalone treatment and in conjunction with other pharmaceutical agents. Cell viability was measured using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, apoptosis was assessed through flow cytometry, and the effects on signaling pathways were analyzed using RNA sequencing and Western blot techniques. Furthermore, a subcutaneous tumor model was utilized to assess the in vivo efficacy of combination therapy on tumor growth. The results of our study suggest that PX may activate the Ca2+-dependent mitochondria-mediated intrinsic apoptosis pathway in TNBC by potentially influencing the PI3K/AKT/mTOR pathway as well as by inducing cytoprotective autophagy. Additionally, the combination of PX and chemotherapeutic agents demonstrated moderate inhibitory effects on 4T1 tumor growth in an in vivo model. These findings indicate that PX may exert its effects on TNBC through modulation of critical molecular pathways, offering important implications for improving chemosensitivity and identifying potential therapeutic combinations for clinical use.

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Section: Resultsmentioning

confidence: 99%

Inhibition of TNBC Cell Growth by Paroxetine: Induction of Apoptosis and Blockage of Autophagy Flux

Huang,

Wu,

et al. 2024

Cancers

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“…Furthermore, necroptosis is involved in other neurodegenerative diseases, such as spinal cord injury (SCI) and retinal degeneration [ 112 , 113 ]. Reactive astrocytes and microglia express more RIPK3 and phosphorylated MLKL after SCI, and astrocytic death is significantly reduced in RIPK3 deficiency mice after SCI [ 94 ].…”

Section: Diseases Involving Ripk3mentioning

confidence: 99%

RIPK3 signaling and its role in regulated cell death and diseases

Zhou,

Xiang,

Liu

et al. 2024

Cell Death Discov.

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Receptor-interacting protein kinase 3 (RIPK3), a member of the receptor-interacting protein kinase (RIPK) family with serine/threonine protein kinase activity, interacts with RIPK1 to generate necrosomes, which trigger caspase-independent programmed necrosis. As a vital component of necrosomes, RIPK3 plays an indispensable role in necroptosis, which is crucial for human life and health. In addition, RIPK3 participates in the pathological process of several infections, aseptic inflammatory diseases, and tumors (including tumor-promoting and -suppressive activities) by regulating autophagy, cell proliferation, and the metabolism and production of chemokines/cytokines. This review summarizes the recent research progress of the regulators of the RIPK3 signaling pathway and discusses the potential role of RIPK3/necroptosis in the aetiopathogenesis of various diseases. An in-depth understanding of the mechanisms and functions of RIPK3 may facilitate the development of novel therapeutic strategies.

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“…Necroptosis is a programmed cell death process that involves the activation of mixed lineage kinase domain-like protein (MLKL)/pMLKL by receptor-interacting protein kinase 1 (RIPK1)/receptor-interacting protein kinase 3 (RIPK3)-mediated phosphorylation signaling pathway. [31,32] The cell death pattern of necroptosis is characterized by lysosomal membrane decline, cytoplasmic vacuolization, plasma membrane disassembly, and cellular rupture, and is driven by the kinase activity of RIPK1. TNF-𝛼 binding to TNFR1 recruits downstream protein molecules to form complex I, including TRADD, RIPK1, cellular inhibitor of apoptosis proteins, TRAF2/5, and LU-BAC proteins.…”

Section: Overview Of Necroptosismentioning

confidence: 99%

Ferroptosis, Necroptosis, and Pyroptosis in Gastrointestinal Cancers: The Chief Culprits of Tumor Progression and Drug Resistance

Zhu

2023

Advanced Science

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In recent years, the incidence of gastrointestinal cancers is increasing, particularly in the younger population. Effective treatment is crucial for improving patients’ survival outcomes. Programmed cell death, regulated by various genes, plays a fundamental role in the growth and development of organisms. It is also critical for maintaining tissue and organ homeostasis and takes part in multiple pathological processes. In addition to apoptosis, there are other types of programmed cell death, such as ferroptosis, necroptosis, and pyroptosis, which can induce severe inflammatory responses. Notably, besides apoptosis, ferroptosis, necroptosis, and pyroptosis also contribute to the occurrence and development of gastrointestinal cancers. This review aims to provide a comprehensive summary on the biological roles and molecular mechanisms of ferroptosis, necroptosis, and pyroptosis, as well as their regulators in gastrointestinal cancers and hope to open up new paths for tumor targeted therapy in the near future.

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Targeting Necroptosis: A Novel Therapeutic Option for Retinal Degenerative Diseases

Cited by 23 publications

References 193 publications

Inhibition of TNBC Cell Growth by Paroxetine: Induction of Apoptosis and Blockage of Autophagy Flux

Inhibition of TNBC Cell Growth by Paroxetine: Induction of Apoptosis and Blockage of Autophagy Flux

RIPK3 signaling and its role in regulated cell death and diseases

Ferroptosis, Necroptosis, and Pyroptosis in Gastrointestinal Cancers: The Chief Culprits of Tumor Progression and Drug Resistance

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