Kaempferol-induced mitochondrial damage promotes NF-κB- NLRP3-caspase-1 signaling axis-mediated pyroptosis in gastric cancer cells DOI Creative Commons

Xiafei Qi,

Jiatong Liu,

liuxiang Wang

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 31, 2023

Abstract Purpose：Gastric cancer （GC）is a gastrointestinal tumor with high morbidity and mortality. Owing to the rate of postoperative recurrence associated GC, effectiveness radiotherapy chemotherapy may be compromised by occurrence severe undesirable side effects. In light these circumstances, kaempferol (KP), flavonoid abundantly present in diverse herbal fruit sources, emerges as promising therapeutic agent inherent anti-tumor properties. This study endeavors demonstrate potential KP context Gastric while unraveling intricate underlying mechanisms. Methods：We employed methods bioinformatics, network pharmacology, molecular docking, followed multiple experimental validations. Result：Our investigations unveil that stimulation effectively promotes activation NLRP3 inflammatory vesicles within AGS cells engaging NF-κB signaling pathway. Consequently, signal cascade triggers cleavage Caspase-1, culminating liberation IL-18. Furthermore, we ascertain facilitate cell pyroptosis inducing mitochondrial damage. Conclusion：Our findings showcase compelling candidate for treatment -related diseases, heralding new possibilities future interventions.

Language: Английский

Crosstalk between non-coding RNAs and programmed cell death in colorectal cancer: implications for targeted therapy DOI Creative Commons
Seyed Reza Taha, Mehdi Karimi, Bahar Mahdavi

et al.

Epigenetics & Chromatin, Journal Year: 2025, Volume and Issue: 18(1)

Published: Jan. 15, 2025

Colorectal cancer (CRC) remains one of the most common causes cancer-related mortality worldwide. Its progression is influenced by complex interactions involving genetic, epigenetic, and environmental factors. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding (lncRNAs), circular (circRNAs), have been identified as key regulators gene expression, affecting diverse biological processes, notably programmed cell death (PCD). This review aims to explore relationship between ncRNAs PCD in CRC, focusing on how influence survival, proliferation, treatment resistance. A comprehensive literature analysis was conducted examine recent findings role modulating various mechanisms, apoptosis, autophagy, necroptosis, pyroptosis, their impact CRC development therapeutic response. were found significantly regulate pathways, impacting tumor growth, metastasis, sensitivity CRC. Their these pathways highlights potential biomarkers for early detection targets innovative interventions. Understanding involvement regulation offers new insights into biology. The targeted modulation ncRNA-PCD presents promising avenues personalized treatment, which may improve patient outcomes enhancing effectiveness reducing

Language: Английский

Citations

1
Multiomics characterization of pyroptosis in the tumor microenvironment and therapeutic relevance in metastatic melanoma DOI Creative Commons
Wenqiong Chen,

Yi He,

Guowei Zhou

et al.

BMC Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 17, 2024

Abstract Background Pyroptosis, mediated by gasdermins with the release of multiple inflammatory cytokines, has emerged as playing an important role in targeted therapy and immunotherapy due to its effectiveness at inhibiting tumor growth. Melanoma is one most commonly used models for development, though inadequate immune response can occur. Moreover, development pyroptosis-related combinations other therapeutic strategies limited insufficient understanding pyroptosis context different microenvironments (TMEs). Methods Here, we present a computational model (pyroptosis-related gene score, PScore) assess status. We applied PScore 1388 melanoma samples our in-house cohort eight publicly available independent cohorts then calculated prognostic power potential predictive marker efficacy. Furthermore, performed association analysis characteristics TME using bulk, single-cell, spatial transcriptomics assessed mutation status, which contributes therapy. Results Pyroptosis-related genes (PRGs) showed distinct expression patterns ability melanoma. Most PRGs were associated better survival metastatic Our based on prognosis exhibits robust performance prediction cohorts. also found be BRAF correlate positively molecular signatures, such KRAS signaling IFN gamma pathway. Based data, immune-enriched had higher than immune-depleted or fibrotic TME. Additionally, monocytes highest malignant cells fibroblasts lowest single-cell transcriptome analyses. Finally, was efficacy checkpoint blockade, suggesting serve response. Conclusions Collectively, findings indicate that factor melanoma, multiomics data. results provide theoretical basis drug combination reveal markers.

Language: Английский

Citations

6
Research progress on molecular mechanism of pyroptosis caused by Helicobacter pylori in gastric cancer DOI Open Access

Yulan Gu,

Yeqiong Xu,

Ping Wang

et al.

Annals of Medicine and Surgery, Journal Year: 2024, Volume and Issue: 86(4), P. 2016 - 2022

Published: Feb. 14, 2024

Gastric cancer (GC) is a prevalent malignancy worldwide. Helicobacter pylori ( H. ), Gram-negative spiral bacterium, has the ability to colonize and persist in human gastric mucosa. Persistent infection been identified as major risk factor for ~80% of GC cases. The interplay between pathogenicity, genetic background, environmental factors collectively contribute transformation. Eradicating beneficial reducing recurrence residual cancer. However, underlying molecular mechanisms involved remain incompletely understood. Additionally, reshapes immune microenvironment within stomach which may compromise immunotherapy efficacy infected individuals. Clinical eradication still faces numerous challenges. In this review, authors summarize recent research progress on elucidating development. Notably, CagA protein—a carcinogenic virulence predominantly expressed by Asian strains —induces inflammation excessive ROS production mucosa cells. Dysregulation multiple pyroptosis signalling pathways can lead malignant transformation these MiRNA-1290 plays crucial role initiation progression while serving an indicator disease dynamics. Pyroptosis exhibits dual roles both promoting carcinogenesis inhibiting tumour growth; thus it holds potential clinical applications drug-resistant treatment strategies. Furthermore, play regulatory system during Lastly, provide overview current concepts regarding well insights into miRNA-1290’s pathogenicity value associated with GC, aiming serve reference material researchers.

Language: Английский

Citations

6
Kaempferol-induced mitochondrial damage promotes NF-κB-NLRP3-caspase-1 signaling axis-mediated pyroptosis in gastric cancer cells DOI Creative Commons

Xiafei Qi,

Jiatong Liu,

Liuxiang Wang

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(7), P. e28672 - e28672

Published: March 23, 2024

GC is a gastrointestinal tumor with high morbidity and mortality. Owing to the rate of postoperative recurrence associated GC, effectiveness radiotherapy chemotherapy may be compromised by occurrence severe undesirable side effects. In light these circumstances, KP, flavonoid abundantly present in diverse herbal fruit sources, emerges as promising therapeutic agent inherent anti-tumor properties. This study endeavors demonstrate potential KP context while unraveling intricate underlying mechanisms. Notably, our investigations unveil that stimulation effectively promotes activation NLRP3 inflammatory vesicles within AGS cells engaging NF-κB signaling pathway. Consequently, signal cascade triggers cleavage Caspase-1, culminating liberation IL-18. Furthermore, we ascertain facilitate cell pyroptosis inducing mitochondrial damage. Collectively, findings showcase compelling candidate for treatment GC-related diseases, heralding new possibilities future interventions.

Language: Английский

Citations

4
Inorganic Nanobiomaterials Boost Tumor Immunotherapy: Strategies and Applications DOI
Qi Meng, Binbin Ding,

Ping’an Ma

et al.

Accounts of Chemical Research, Journal Year: 2025, Volume and Issue: unknown

Published: April 3, 2025

ConspectusTumor immunotherapy, as a new antitumor method to fight cancer by activating or enhancing the body's own immune system, has been extensively studied and applied in clinical practice. However, an extremely complex tumor heterogeneity immunosuppressive microenvironment (TME) lead poor response rate secondary drug resistance. The advent of nanotechnology ushered era for immunotherapy. In particular, inorganic nanomaterials, with their unique physicochemical properties excellent biocompatibility, are becoming important tool Inorganic nanomaterials can be used carriers agents, improving delivery efficiency thereby reducing systemic immunotoxicity responses. also trigger immunogenic cell death (ICD), stimulate responses, alleviate TME increasing oxygen levels, modulating metabolic pathways, altering secretion cytokines. synergistic integration immunotherapy adeptly navigates around constraints conventional treatments, side effects while concurrently augmenting therapeutic efficacy. this review, we summarize our recent efforts design synthesis nanobiomaterials enhance efficacy These achieve desired mainly through four strategies, including inducing ICD, developing nanovaccines, pyroptosis, regulating metabolism, providing beneficial implications For one thing, due deficiency ICD effect single therapy, developed nanocatalysts that integrate multiple functions play catalytic role TME, converting substances metabolites into products situ, further ICD. another, order solve problems low antigen loading existing adjuvants, several novel multifunctional nanoadjuvants were prepared, which combine high multimode function one, efficient activation. Moreover, attain strong inflammatory responses immunogenicity, engineer pyroptosis adjuvants selectively induce intracellular oxidative stress ion overload. Finally, reverse microenvironment, nanoplatforms target levels nutrients such glucose, lactic acid, citric tryptophan effectively alter response. implementation these strategies not only improves but reduces provides valuable insights references development assist

Language: Английский

Citations

0
Cell Death Modalities in Therapy of Melanoma DOI Open Access
Meng Wang, Jiahui Zhao,

Ming Tang

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3475 - 3475

Published: April 8, 2025

Melanoma, one of the most lethal cancers, demands urgent and effective treatment strategies. However, a successful therapeutic approach requires precise understanding mechanisms underlying melanoma initiation progression. This review provides an overview pathogenesis, identifies current pathogenic factors contributing to mortality, explores targeted therapy checkpoint inhibitor therapy. Furthermore, we examine classification corresponding therapies, along with advancements in various cell death for treatment. We also discuss status some drawbacks encountered during research stages such as resistance metastasis.

Language: Английский

Citations

0
K-Homology Splicing Regulatory Protein (KSRP) Augments Survival and Proliferation of Human Melanoma Cells DOI Creative Commons
Harunur Rashid, Mohammad Asif Sherwani,

Jung Vin Seo

et al.

Current Issues in Molecular Biology, Journal Year: 2025, Volume and Issue: 47(5), P. 356 - 356

Published: May 13, 2025

Melanoma is one of the most aggressive and fatal cancers; however, effective long-lasting treatment options for melanoma continue to be sought after due development resistance mechanisms currently available therapies. Background: The K-homology-type splicing regulatory protein (KSRP) an RNA-binding that binds AU-rich elements at 3′-UTR target mRNAs. Prior studies have demonstrated KSRP plays a crucial role in post-transcriptional regulation gene expression human melanoma. Subsequently, this study, we further examined cell migration, colony formation, apoptosis, tumorigenicity Methods: was knocked down two different lines: A375 SK-MEL-28, using lenti-shRNA techniques. By doing so, studied effects inhibition on proliferation, these lines. Results: We observed significant decrease tumorigenicity, while also observing substantial increase apoptosis knock Conclusions: Our data establishes vital both SK-MEL-28

Language: Английский

Citations

0
Pyroptosis: Induction and inhibition strategies for immunotherapy of diseases DOI Creative Commons
Junjun Wu, Hong Wang, Pu Gao

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(10), P. 4195 - 4227

Published: June 28, 2024

Cell death is a central process for organismal health. Pyroptosis, namely pyroptotic cell death, recognized as critical type that disrupts membrane and triggers pro-inflammatory cytokine secretion

Language: Английский

Citations

3
The Role and Therapeutic Potential of Pyroptosis in Colorectal Cancer: A Review DOI Creative Commons

Qing Fang,

Yunhua Xu,

Xiangwen Tan

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(7), P. 874 - 874

Published: July 20, 2024

Colorectal cancer (CRC) is one of the leading causes cancer-related mortality worldwide. The unlimited proliferation tumor cells key features resulting in malignant development and progression CRC. Consequently, understanding potential growth molecular mechanisms developing effective therapeutic strategies have become CRC treatment. Pyroptosis an emerging type regulated cell death (RCD) that has a significant role growth. For last few years, numerous studies indicated close correlation between pyroptosis occurrence, progression, treatment many malignancies, including to inhibit area Thus, this review mainly summarized different pathways mechanisms, anti-tumor (tumor suppressor) protective roles CRC, clinical prognostic value which may contribute exploring new for

Language: Английский

Citations

2
Nanomaterials‐Induced PANoptosis: A Promising Anti‐Tumor Strategy DOI

Guanghui Hou,

Youdong Chen,

Huali Lei

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 19, 2024

Abstract Malignant tumors pose a significant threat to global public health. Promoting programmed cell death in cancer cells has become critical strategy for treatment. PANoptosis, newly discovered form of regulated death, integrates key molecular components pyroptosis, apoptosis, and necroptosis, activating these three pathways simultaneously achieve synergistic multi‐mechanistic killing. PANoptosis significantly inhibits growth resistance activates strong anti‐tumor immune response, making tumor‐specific induction potential therapeutic strategy. Currently, treatment research related is focused mainly on the development small molecules cytokines. However, approaches still face limitations terms metabolic stability tumor specificity. The unique physicochemical properties biological activities nanomaterials hold promise optimizing strategies. This review summarizes concept mechanisms highlights latest applications nanoagents PANoptosis‐based anti‐cancer therapy, discusses challenges future directions clinical translation. It hoped that this will inspire further exploration treatments, providing new perspectives researchers field.

Language: Английский

Citations

2