Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown
Published: May 1, 2025
Language: Английский
Heliyon, Journal Year: 2024, Volume and Issue: 10(12), P. e32899 - e32899
Published: June 1, 2024
Natural products are being developed as possible treatment options due to the rising prevalence of cancer and harmful side effects synthetic medications. Arctiin is a naturally occurring lignan found in numerous plants exhibits different pharmacological activities, along with cancer. To elucidate anticancer properties underlying mechanisms action, comprehensive search various electronic databases was conducted using appropriate keywords identify relevant publications. The findings suggest that arctiin against tumor formation cancers such cervical, myeloma, prostate, endothelial, gastric, colon several preclinical investigations. This compound exerts its effect through cellular mechanisms, including mitochondrial dysfunction, cell cycle at phases (G2/M), inhibition proliferation, apoptotic death, cytotoxic effects, well migration invasion malignant cells. Moreover, study also revealed that, among pathways, shown be more potent terms PI3K/AKT JAK/STAT signaling pathways. However, pharmacokinetic investigation indicated compound's poor oral bioavailability. Because these findings, might considered promising chemotherapeutic drug candidate.
Language: Английский
Citations
16
Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(6)
Published: May 28, 2024
Abstract Background Although numerous studies have indicated that activated pyroptosis can enhance the efficacy of antitumour therapy in several tumours, precise mechanism colorectal cancer (CRC) remains unclear. Methods Pyroptosis CRC cells treated with agents was assessed using various techniques, including Western blotting, lactate dehydrogenase release assay and microscopy analysis. To uncover epigenetic mechanisms regulate NLRP3, chromatin changes NLRP3 promoter histone modifications were Assay for Transposase‐Accessible Chromatin sequencing RNA sequencing. immunoprecipitation‒quantitative polymerase chain reaction used to investigate transcriptional regulatory mechanism. Additionally, xenograft patient‐derived models constructed validate effects drug combinations. Results As core molecule inflammasome, expression silenced CRC, thereby limiting gasdermin D (GSDMD)‐mediated pyroptosis. Supplementation rescue induced by therapy. Overexpression HDAC2 silences via regulation. Mechanistically, suppressed accessibility eliminating H3K27 acetylation. knockout promotes H3K27ac‐mediated recruitment BRD4‐p‐P65 complex transcription. Inhibiting Santacruzamate A combination classic (5‐fluorouracil or regorafenib) xenograft‐bearing animals markedly achieved a significant therapeutic effect. Clinically, is inversely correlated H3K27ac/p‐P65/NLRP3 prognostic factor patients. Conclusion Collectively, our data revealed crucial role inhibiting NLRP3/GSDMD‐mediated highlighted as potential target Highlights Silencing limits GSDMD‐dependent cancer. HDAC2‐mediated deacetylation leads silencing NLRP3. suppresses transcription formation H3K27ac/BRD4/p‐P65 complex. Targeting activates enhances
Language: Английский
Citations
12
Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 175, P. 116673 - 116673
Published: May 6, 2024
Multiple sclerosis (MS) is a complex autoimmune disorder that impacts the central nervous system (CNS), resulting in inflammation, demyelination, and neurodegeneration. The NOD-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome, multiprotein of innate immune system, serves an essential role pathogenesis MS by regulating production pro-inflammatory cytokines (IL-1β & IL-18) induction pyroptotic cell death. Mitochondrial dysfunction one main potential factors can trigger NLRP3 inflammasome activation lead to inflammation axonal damage MS. This highlights importance understanding how mitochondrial dynamics modulate activity contribute inflammatory neurodegenerative features lack comprehensive urge for introduction new therapeutic strategies led us review targeting interplay between paper also evaluates natural synthetic compounds improve function and/or inhibit thereby providing neuroprotection. Moreover, it summarizes evidence from animal models demonstrate beneficial effects these on reducing Finally, this advocates deeper investigation into molecular crosstalk as means refine targets
Language: Английский
Citations
9
International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2716 - 2716
Published: March 18, 2025
Understanding how different contributors within the tumor microenvironment (TME) function and communicate is essential for effective cancer detection treatment. The TME encompasses all surroundings of a such as blood vessels, fibroblasts, immune cells, signaling molecules, exosomes, extracellular matrix (ECM). Subsequently, therapy relies on addressing alterations, known drivers progression, evasion, metastasis. Immune cells other cell types act differently under cancerous conditions, either driving or hindering progression. For instance, tumor-infiltrating lymphocytes (TILs) include B T that can invade malignancies, bringing in enhancing ability system to recognize destroy cells. Therefore, TILs display promising approach tackling alterations have capability significantly hinder Similarly, exosomes inflammasomes exhibit dual effect, resulting progression inhibition depending origin type inflammasome tumor. This review will explore presence tumor, communication between role TILs, TME. efforts this are aimed at garnering interest safer durable therapies cancer, addition providing avenue advancing consequently improving survival rates.
Language: Английский
Citations
1
Critical Reviews in Oncology/Hematology, Journal Year: 2024, Volume and Issue: 197, P. 104340 - 104340
Published: April 1, 2024
Pyroptosis can be triggered through both canonical and non-canonical inflammasome pathways, involving the cleavage of gasdermin (GSDM) protein family members, like GSDMD GSDME. The impact pyroptosis on tumors is nuanced, because its role in regulating cancer progression anti-tumor immunity may vary depending tumor type, stage, location, immune status. However, cannot simply categorized as promoting or inhibiting based solely whether it acute chronic nature. interplay between intricate, with some evidence suggesting that facilitate growth, while induction could stimulate anti-cancer responses. Tumor hypoxia activates inducible factor (HIF) signaling to modulate checkpoint expression. Targeting this hypoxia-pyroptosis-immune escape axis a promising therapeutic strategy. This review highlights complex crosstalk hypoxia, pyroptosis, evasion TME.
Language: Английский
Citations
7
British Journal of Pharmacology, Journal Year: 2024, Volume and Issue: unknown
Published: Oct. 12, 2024
Abstract Inflammation has a pivotal role in the initiation and progression of various cancers, contributing to crucial processes such as metastasis, angiogenesis, cell proliferation invasion. Moreover, release cytokines mediated by inflammation within tumour microenvironment (TME) orchestrating these events. The activation inflammatory caspases, facilitated recruitment caspase‐1, is initiated pattern recognition receptors on immune membrane. This results production proinflammatory cytokines, including IL‐1β IL‐18, participates diverse biological with significant implications. NOD‐Like Receptor Protein 3 (NLRP3) inflammasome holds central innate immunity regulates through releasing IL‐18. it interacts cellular compartments. Recently, mechanisms underlying NLRP3 have garnered considerable attention. Disruption been associated spectrum diseases, encompassing diabetes, enteritis, neurodegenerative obesity tumours. impact tumorigenesis varies across different cancer types, contrasting roles observed. For example, colorectal colitis can be suppressed NLRP3, whereas gastric skin cancers may promoted its activity. review provides comprehensive insights into structure, characteristics inflammasome, specific focus relationship between tumour‐related responses, TME. Furthermore, explores potential strategies for targeting via modulation. encompasses innovative approaches, NLRP3‐based nanoparticles, gene‐targeted therapy checkpoint inhibitors.
Language: Английский
Citations
5
Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)
Published: Oct. 21, 2024
Abstract Chronic inflammation and NLRP3 inflammasome activation are among the determining factors of breast malignancies. Paclitaxel (PTX) is a drug used in cancer treatment which sustains prolonged inflammation, reducing effectiveness chemotherapy. Considering impact inflammatory processes progression, there strong concern to develop therapeutic strategy targeting for triple-negative (TNBC) treatment. Therefore, aim this study was evaluate potential PTX modulation counterbalance TNBC by inducing programmed cell death inhibiting activity pro-inflammatory cytokines. The obtained results suggested interaction between revealed that pharmacological inhibition, using NLRP3-specific inhibitor MCC950, genetic silencing specific small interfering RNA, reduced responses facilitated PTX-determined tumor death. Thus, manipulation combination with anti-tumor drugs opens up new perspectives therapy.
Language: Английский
Citations
5
Cells, Journal Year: 2024, Volume and Issue: 13(3), P. 233 - 233
Published: Jan. 25, 2024
IL-1 family members have multiple pleiotropic functions affecting various tissues and cells, including the regulation of immune response, hematopoietic homeostasis, bone remodeling, neuronal physiology, synaptic plasticity. Many these activities are involved in pathological processes immunological disorders, tumor initiation progression. Indeed, been described to contribute shaping microenvironment (TME), determining evasion drug resistance, sustain aggressiveness metastasis. This review addresses role sarcomas, particularly highly metastatic osteosarcoma (OS) Ewing sarcoma (EWS), discusses IL-1-family-related mechanisms that play a metastasis development. We also consider therapeutic implications targeting members, which proposed as (i) relevant targets for anti-tumor anti-metastatic drugs; (ii) checkpoints suppression; (iii) potential antigens immunotherapy.
Language: Английский
Citations
4
Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(3), P. 299 - 299
Published: Feb. 26, 2024
The NLR family pyrin domain containing 3 (NLRP3) promotes the growth of colorectal cancer (CRC). However, therapeutic effect NLRP3 inhibition on CRC cell progression is controversial. This study comparatively investigated a pharmacological inhibitor, glibenclamide (gli), and post-translational suppression by miR-223 in HCT-116 HCT-15 cells. LPS ATP were used to activate Gli-treated LSB-hsa-miR-223-3p (WTmiR-223)-expressing NLRP3.AB.pCCL.sin.cPPT.U6.miR-223-Decoy.hPGK.GFP.WPRE plasmid (DmiR-223) was negative control for expression. NLRP3, gasdermin D, BAX expressions analyzed using western blotting. Real-time PCR detected RNA expression autophagy-related genes ATG5, BECN1, non-transfected ELISA IL-1β IL-18 medium. MTS-1, annexin V, wound-healing, sphere-invasion assays assess viability progression. A multiplex cytokine assay proinflammatory secretion. LPS–ATP-activated produced D cleavage, released IL-1b IL-18, activated migration sphere invasion. In contrast, reduced growth, expression, IFN-γ, CXCL10, LIF secretion found cells after inflammasome activation. Both gli WTmiR-223 induced autophagy ATG5 BECN1 activation its downstream proteins. while had limited production LIF, increased release those cytokines. addition, did not suppress promoted apoptosis. Notably, neither nor effectively prevented These data suggest that, could have better anticancer compared gli, sole usage miR-223-mediated may be sufficient prevent metastasis.
Language: Английский
Citations
4
Pathology - Research and Practice, Journal Year: 2024, Volume and Issue: 260, P. 155444 - 155444
Published: Aug. 1, 2024
Language: Английский
Citations
4