Pyroptosis and Its Role in Cervical Cancer

Li, Kangchen; Qiu, Jia-Ling; Pan, Jun; Pan, Jianping

doi:10.3390/cancers14235764

Cited by 8 publications

(4 citation statements)

References 100 publications

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“…In contrast, similar to apoptotic cells, necroptotic cells may exhibit PS on the outer membrane. Furthermore, as discussed earlier, TNF is the most well-known cytokine triggering the necroptosis pathway [ 67 , 68 , 69 ]. The above-mentioned findings suggest that the cell death observed following treatment with MM -compounds may be a combination of both apoptosis and necroptosis, depending on the cell type, incubation time, and compound concentration ( Figure 12 ).…”

Section: Discussionmentioning

confidence: 99%

Pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine Sulfonamides as an Important Scaffold for Anticancer Drug Discovery—In Vitro and In Silico Evaluation

Kciuk

Marciniak

Çeli̇k

et al. 2023

IJMS

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Pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine sulfonamides (MM-compounds) are a relatively new class of heterocyclic compounds that exhibit a wide variety of biological actions, including anticancer properties. Here, we used caspase enzyme activity assays, flow cytometry analysis of propidium iodide (PI)-stained cells, and a DNA laddering assay to investigate the mechanisms of cell death triggered by the MM-compounds (MM134, -6, -7, and -9). Due to inconsistent results in caspase activity assays, we have performed a bromodeoxyuridine (BrdU) incorporation assay, colony formation assay, and gene expression profiling. The compounds’ cytotoxic and pro-oxidative properties were also assessed. Additionally, computational studies were performed to demonstrate the potential of the scaffold for future drug discovery endeavors. MM-compounds exhibited strong micromolar (0.06–0.35 µM) anti-proliferative and pro-oxidative activity in two cancer cell lines (BxPC-3 and PC-3). Activation of caspase 3/7 was observed following a 24-h treatment of BxPC-3 cells with IC50 concentrations of MM134, -6, and -9 compounds. However, no DNA fragmentation characteristics for apoptosis were observed in the flow cytometry and DNA laddering analysis. Gene expression data indicated up-regulation of BCL10, GADD45A, RIPK2, TNF, TNFRSF10B, and TNFRSF1A (TNF-R1) following treatment of cells with the MM134 compound. Moreover, in silico studies indicated AKT2 kinase as the primary target of compounds. MM-compounds exhibit strong cytotoxic activity with pro-oxidative, pro-apoptotic, and possibly pro-necroptotic properties that could be employed for further drug discovery approaches.

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Section: Discussionmentioning

confidence: 99%

Pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine Sulfonamides as an Important Scaffold for Anticancer Drug Discovery—In Vitro and In Silico Evaluation

Kciuk

Marciniak

Çeli̇k

et al. 2023

IJMS

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“…Elevated SIRT1 expression inhibits the AIM2 inflammasome, a mechanism that suppresses pyroptosis while promoting the proliferation of cancer cells. Providing EVs with AIM2 inflammasome proteins was found to induce pyroptosis in cancer cells by downregulating SIRT1 [ 121 , 122 ]. Necroptosis acts as an alternative form of programmed cell death that surpasses resistance to apoptosis, and has the potential to initiate and enhance immune responses against tumors in cancer treatment.…”

Section: Evs As Integrators Of Homeostasismentioning

confidence: 99%

Utilizing Extracellular Vesicles for Eliminating ‘Unwanted Molecules’: Harnessing Nature’s Structures in Modern Therapeutic Strategies

Kisielewska,

Rakoczy,

Skowron

et al. 2024

Molecules

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Extracellular vesicles (EVs) are small phospholipid bilayer-bond structures released by diverse cell types into the extracellular environment, maintaining homeostasis of the cell by balancing cellular stress. This article provides a comprehensive overview of extracellular vesicles, their heterogeneity, and diversified roles in cellular processes, emphasizing their importance in the elimination of unwanted molecules. They play a role in regulating oxidative stress, particularly by discarding oxidized toxic molecules. Furthermore, endoplasmic reticulum stress induces the release of EVs, contributing to distinct results, including autophagy or ER stress transmission to following cells. ER stress-induced autophagy is a part of unfolded protein response (UPR) and protects cells from ER stress-related apoptosis. Mitochondrial-derived vesicles (MDVs) also play a role in maintaining homeostasis, as they carry damaged mitochondrial components, thereby preventing inflammation. Moreover, EVs partake in regulating aging-related processes, and therefore they can potentially play a crucial role in anti-aging therapies, including the treatment of age-related diseases such as Alzheimer’s disease or cardiovascular conditions. Overall, the purpose of this article is to provide a better understanding of EVs as significant mediators in both physiological and pathological processes, and to shed light on their potential for therapeutic interventions targeting EV-mediated pathways in various pathological conditions, with an emphasis on age-related diseases.

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“…Moreover, pyroptosis activation by inhibiting SF3B1 improves the development of ovarian cancer 13 . Additionally, recent research has shown pyroptosis is directly associated with the beginning and development of CC 14 . Therefore, it is worth figuring out more novel molecules involved in pyroptotic pathways linked to CC.…”

Section: Introductionmentioning

confidence: 99%

KIF23 promotes cervical cancer progression via inhibiting NLRP3‐mediated pyroptosis

Liu,

Xie,

et al. 2024

The FASEB Journal

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BackgroundCervical cancer (CC), closely linked to persistent human papillomavirus infection, represents a major health problem for women worldwide. The objective of this study is to elucidate KIF23's role in the development of CC and its regulatory mechanism.MethodsThe bioinformatics methods were utilized to extract pyroptosis‐associated differentially expressed genes (DEGs) and pivot genes from the GSE9750 and GSE63678 datasets, followed by immune infiltration analysis and quantification of these genes' expression. The effects of kinesin family member 23 (KIF23) were verified through functional experiments in vitro and a mouse xenograft model. The NLPR3 activator, nigericin, was applied for further analyzing the potential regulatory mechanism of KIF23 in CC.ResultsA total of 8 pyroptosis‐related DEGs were screened out, among which 4 candidate core genes were identified as candidate hub genes and confirmed upregulation in CC tissues and cells. These genes respectively showed a positive correlation with the infiltration of distinct immune cells or tumor purity. Downregulation of KIF23 could suppress the proliferation, migration, and invasion abilities in CC cells and tumorigenesis through enhancing pyroptosis. Conversely, KIF23 overexpression accelerated the malignant phenotypes of CC cells and inhibited pyroptosis activation, which was blocked by nigericin treatment.ConclusionsKIF23 may play an oncogenic role in CC progression via inhibition of the NLRP3‐mediated pyroptosis pathway.

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Pyroptosis and Its Role in Cervical Cancer

Cited by 8 publications

References 100 publications

Pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine Sulfonamides as an Important Scaffold for Anticancer Drug Discovery—In Vitro and In Silico Evaluation

Pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine Sulfonamides as an Important Scaffold for Anticancer Drug Discovery—In Vitro and In Silico Evaluation

Utilizing Extracellular Vesicles for Eliminating ‘Unwanted Molecules’: Harnessing Nature’s Structures in Modern Therapeutic Strategies

KIF23 promotes cervical cancer progression via inhibiting NLRP3‐mediated pyroptosis

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