The role of pyroptosis in inflammatory diseases

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: May 12, 2023

Programmed cell death has crucial roles in the physiological maturation of an organism, maintenance metabolism, and disease progression. Pyroptosis, a form programmed which recently received much attention, is closely related to inflammation occurs via canonical, non-canonical, caspase-3-dependent, unclassified pathways. The pore-forming gasdermin proteins mediate pyroptosis by promoting lysis, contributing outflow large amounts inflammatory cytokines cellular contents. Although response critical for body’s defense against pathogens, uncontrolled can cause tissue damage vital factor occurrence progression various diseases. In this review, we briefly summarize major signaling pathways discuss current research on pathological function autoinflammatory diseases sterile

Language: Английский

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Pyroptotic cell death: an emerging therapeutic opportunity for radiotherapy

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: Jan. 16, 2024

Abstract Pyroptotic cell death, an inflammatory form of programmed death (PCD), is emerging as a potential therapeutic opportunity for radiotherapy (RT). RT commonly used cancer treatment, but its effectiveness can be limited by tumor resistance and adverse effects on healthy tissues. Pyroptosis, characterized swelling, membrane rupture, release pro-inflammatory cytokines, has been shown to enhance the immune response against cells. By inducing pyroptotic in cells, treatment outcomes stimulating anti-tumor responses improving overall efficacy RT. Furthermore, danger signals from cells promote recruitment activation leading systemic that may target distant metastases. Although further research needed fully understand mechanisms optimize use RT, it holds promise novel strategy outcomes. This review aims synthesize recent regulatory underlying radiation-induced pyroptosis elucidate significance this process The insights gained analysis inform strategies tumors.

Language: Английский

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Therapeutic strategies of targeting non-apoptotic regulated cell death (RCD) with small-molecule compounds in cancer

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(7), P. 2815 - 2853

Published: April 24, 2024

Regulated cell death (RCD) is a controlled form of orchestrated by one or more cascading signaling pathways, making it amenable to pharmacological intervention. RCD subroutines can be categorized as apoptotic non-apoptotic and play essential roles in maintaining homeostasis, facilitating development, modulating immunity. Accumulating evidence has recently revealed that evasion frequently the primary cause tumor survival. Several have garnered attention promising cancer therapies due their ability induce regression prevent relapse, comparable apoptosis. Moreover, they offer potential solutions for overcoming acquired resistance tumors toward drugs. With an increasing understanding underlying mechanisms governing these subroutines, growing number small-molecule compounds targeting single multiple pathways been discovered, providing novel strategies current therapy. In this review, we comprehensively summarized regulatory emerging mainly including autophagy-dependent death, ferroptosis, cuproptosis, disulfidptosis, necroptosis, pyroptosis, alkaliptosis, oxeiptosis, parthanatos, mitochondrial permeability transition (MPT)-driven necrosis, entotic NETotic lysosome-dependent immunogenic (ICD). Furthermore, focused on discussing related compounds. brief, insightful findings may provide valuable guidance investigating individual collaborative approaches towards different ultimately driving discovery target significantly enhance future therapeutics.

Language: Английский

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Therapeutic Effects of Natural Products on Liver Cancer and Their Potential Mechanisms

Nutrients, Journal Year: 2024, Volume and Issue: 16(11), P. 1642 - 1642

Published: May 27, 2024

Liver cancer ranks third globally among causes of cancer-related deaths, posing a significant public health challenge. However, current treatments are inadequate, prompting growing demand for novel, safe, and effective therapies. Natural products (NPs) have emerged as promising candidates in drug development due to their diverse biological activities, low toxicity, minimal side effects. This paper begins by reviewing existing treatment methods drugs liver cancer. It then summarizes the therapeutic effects NPs sourced from various origins on Finally, we analyze potential mechanisms treating cancer, including inhibition angiogenesis, migration, invasion; regulation cell cycle; induction apoptosis, autophagy, pyroptosis, ferroptosis; influence tumor metabolism; immune regulation; intestinal function; key signaling pathways. systematic review aims provide comprehensive overview research treatment, offering foundation further application pharmaceuticals functional foods.

Language: Английский

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Natural products targeting macroautophagy signaling in hepatocellular carcinoma therapy: Recent evidence and perspectives

Phytotherapy Research, Journal Year: 2024, Volume and Issue: 38(3), P. 1623 - 1650

Published: Feb. 1, 2024

Abstract Hepatocellular carcinoma (HCC), presently the second leading cause of global cancer‐related mortality, continues to pose significant challenges in realm medical oncology, impacting both clinical drug selection and mechanistic research. Recent investigations have unveiled autophagy‐related signaling as a promising avenue for HCC treatment. A growing body research has highlighted pivotal role autophagy‐modulating natural products inhibiting progression. In this context, we provide concise overview fundamental autophagy mechanism delineate involvement autophagic pathways development. Additionally, review pertinent studies demonstrating how regulate mitigate HCC. Our findings indicate that exhibit cytotoxic effects through induction excessive autophagy, simultaneously impeding cell proliferation by inhibition, thereby depriving cells essential energy. These been associated with various pathways, including PI3K/AKT, MAPK, AMPK, Wnt/β‐catenin, Beclin‐1, ferroautophagy. results underscore considerable therapeutic potential However, it is important note present study did not establish definitive thresholds or inhibition products. Further domain imperative gain comprehensive insights into dual equipping us better understanding double‐edged sword management.

Language: Английский

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Insights into the Role of Oxidative Stress in Hepatocellular Carcinoma Development

Frontiers in Bioscience-Landmark, Journal Year: 2023, Volume and Issue: 28(11), P. 286 - 286

Published: Nov. 8, 2023

Oxidative stress (OS) is linked to hepatocellular carcinoma (HCC) progression. HCC may develop as a result of genetic changes, including oxidative injury both nuclear and mitochondrial DNA. Signaling pathways regulated by OS, such Wnt/β-catenin Notch pathways, are vital regulators in developing HCC. OS-mediated activation transcription factors, factor-κB p53, among others, capable regulating the redox state cells. OS also affects tumor microenvironment, which, turn, regulates In HCC, reactive oxygen species (ROS) can potentially enhance cell proliferation, metastasis, resistance treatment. However, elevated ROS levels cause cytotoxicity trigger apoptosis This review highlights explores potential stress-related treatment targets offering novel insights for clinical therapies.

Language: Английский

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Ferroptosis, pyroptosis and necroptosis in hepatocellular carcinoma immunotherapy: Mechanisms and immunologic landscape (Review)

International Journal of Oncology, Journal Year: 2024, Volume and Issue: 64(6)

Published: May 9, 2024

Hepatocellular carcinoma (HCC), one of the leading causes cancer‑related mortality worldwide, is challenging to identify in its early stages and prone metastasis, prognosis patients with this disease poor. Treatment options for HCC are limited, even radical treatments being associated a risk recurrence or transformation short term. Furthermore, multi‑tyrosine kinase inhibitors approved first‑line therapy have marked drawbacks, including drug resistance side effects. The rise breakthrough immune checkpoint (ICIs) provided novel direction immunotherapy but these drawback low response rates. Since avoiding apoptosis universal feature cancer, induction non‑apoptotic regulatory cell death (NARCD) strategy immunotherapy. At present, NARCD pathways, ferroptosis, pyroptosis necroptosis, potential forms immunogenic death, which synergistic effects antitumor immunity, transforming 'cold' tumors into 'hot' exerting Therefore, pathways may be targeted as treatment HCC. In present review, roles necroptosis immunity discussed, relevant targets signaling current status combined ICIs summarized. prospects targeting also considered.

Language: Английский

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Crassifolin A prolongs lifespan and healthspan in Caenorhabditis elegans via activating autophagy

Journal of Ethnopharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 119399 - 119399

Published: Jan. 1, 2025

Language: Английский

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Triggering Pyroptosis in Cancer

Biomolecules, Journal Year: 2025, Volume and Issue: 15(3), P. 348 - 348

Published: Feb. 28, 2025

Pyroptosis is an inflammatory programmed cell death recently identified as a crucial cellular process in various diseases, including cancers. Unlike other forms of death, canonical pyroptosis involves the specific cleavage gasdermin by caspase-1, resulting membrane damage and release pro-inflammatory cytokines IL-1β IL-18. Initially observed innate immune cells responding to external pathogens or internal signals, pyroptotic has now been numerous types. Recent studies have extensively explored different ways trigger solid tumors, presenting promising avenue for cancer treatment. This review outlines mechanisms both noncanonical pertinent primarily focuses on biomolecules that can induce malignancies. strategy aims not only eliminate but also promote improved tumor microenvironment. Furthermore, emerging research indicates targeting pathways may improve effectiveness existing treatments, making them more potent against resistant types, offering new hope overcoming treatment resistance aggressive

Language: Английский

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Ginkgolide B Inhibits EMT and Promotes Pyroptosis in Gastric Cancer via AKT/mTOR Pathway

Drug Design Development and Therapy, Journal Year: 2025, Volume and Issue: Volume 19, P. 2491 - 2502

Published: April 1, 2025

Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide, necessitating the exploration novel therapeutic agents to improve patient outcomes. This study elucidates anti-cancer properties Ginkgolide B (GGB), diterpenoid lactone derived from Ginkgo biloba, in both vitro and vivo models GC. Using AGS HGC-27 cell lines, we assessed GGB's impact on cellular proliferation, colony formation, migration, invasion, apoptosis, pyroptosis. GGB exhibited significant dose- time-dependent inhibition proliferation with no cytotoxicity observed normal gastric epithelial cells. Furthermore, markedly suppressed migration induced apoptosis pyroptosis, as evidenced by increased Bax GSDMD expression decreased Bcl-2 levels. In vivo, treatment significantly reduced tumor growth nude mouse xenograft model modulated EMT markers, decreasing PCNA N-cadherin levels while increasing E-cadherin expression. Mechanistically, effects were mediated through deactivation PI3K/AKT/mTOR signaling pathway. These findings underscore potential promising agent for GC, warranting further clinical evaluation.

Language: Английский

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