Esculetin inhibits the pyroptosis of microvascular endothelial cells through NF-κB /NLRP3 signaling pathway

Ren, Wei; Zhou, Qilyu; Yu, Ruyang; Liu, Zhongjie; Hu, Yusheng

doi:10.1016/j.abb.2022.109173

Cited by 5 publications

(6 citation statements)

References 22 publications

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“…Ferritinophagy results in iron overload in tumour cells, which promotes tumour cell ferroptosis. [48][49][50] Esculetin is a natural dihydroxy coumarin that is distributed in a variety of plants, [21][22][23][24][25] such as marine sponge. Studies showed that it has inhibitory effects on various tumours and its antitumoral mechanism involves the activation of cellular processes, such as apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…Studies showed that it has inhibitory effects on various tumours and its antitumoral mechanism involves the activation of cellular processes, such as apoptosis. [24][25][26][27][28][29][30][31][32] However, esculetin's effects of activating ferritinophagy in liver cancer to has never been studied and its mechanism is unidentified.…”

Section: Discussionmentioning

confidence: 99%

“…It also has antibacterial and anti-inflammatory effects. [22][23][24][25] In recent years, esculetin has garnered extensive attention for its use in tumour therapy, as it has been shown to have therapeutic effects on leukaemia, glioma, prostate, colon, pancreatic, melanoma, breast and gastric cancers, [24][25][26][27][28][29][30][31][32] Some researchers found that esculetin induces ROS formation and activates apoptosis in gastric cancer cells. 33 Esculetin acts on PGK2, GPD2 and GPI to prevent cancer cells from undergoing glycolysis.…”

Section: Introductionmentioning

confidence: 99%

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Inhibitory Effects of Esculetin on Liver Cancer Through Triggering NCOA4 Pathway-Mediation Ferritinophagy in vivo and in vitro

Xiu¹,

Li²,

Fang³

et al. 2023

JHC

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Objective To explore the effects of Esculetin on liver cancer and explore potential mechanisms of Esculetin-inducing cells death. Methods Esculetin’s effects on the proliferation, migration and apoptosis of HUH7 and HCCLM3 cells were detected by using CCK8, crystal violet staining, wound healing, Transwell TM and Annexin V-FITC/PI. Flow cytometry, fluorescence staining, Western blot, T-AOC, DPPH radical scavenging assay, hydroxyl radical’s inhibitory capability and GSH test were used to examine the esculetin’s effects on the ROS level, the oxidation-related substances and proteins’ expression in hepatoma cells. In vivo experiment was performed by xenograft model. Ferrostatin-1 was used to determine the death way of hepatoma cells induced by esculetin. Live cell probe, Western blot, Fe 2+ content, MDA, HE staining, Prussian blue staining and immunohistochemistry were used to examine the ferritinophagy-related phenomenon induced by esculetin in hepatoma cells. The relationship between esculetin and NCOA4-mediated ferritinophagy was confirmed through gene silence and overexpression, immunofluorescence staining and Western blot. Results Esculetin suppressed the proliferation, migration and apoptosis of HUH7 and HCCLM3 cells significantly, influenced the oxidative stress level, altered the autophagy and iron metabolism levels in cells, and produced a ferritinophagy-related phenomena. Esculetin increased the levels of cellular lipid peroxidation and reactive oxygen species. In vivo, esculetin could decrease tumour volume, promote LC3 and NCOA4 expressions, suppresse hydroxyl radical‘s inhibiting capacity and GSH, increase Fe 2+ and MDA levels, decrease antioxidant proteins expression in tumour tissue. In addition, Esculetin could also increase the iron deposition of tumour tissues, promote ferritinophagy, and induce tumours’ ferroptosis. Conclusion Esculetin has an inhibitory effect on liver cancer in vivo and in vitro through triggering NCOA4 pathway-mediation ferritinophagy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Inhibitory Effects of Esculetin on Liver Cancer Through Triggering NCOA4 Pathway-Mediation Ferritinophagy in vivo and in vitro

Xiu¹,

Li²,

Fang³

et al. 2023

JHC

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“… [ 86 ] Esculetin Inhibition of pyroptosis through NF-κB/NLRP3 signaling pathway. [ 87 ] Activators Curcumin It activates NLRC4, AIM2, and IFI16 inflammasomes and induces pyroptosis via upregulated ISG3 transcription factors in leukemic cells. [ 88 ] Cathepsin B Activation of NLRP3/caspase-1-induced pyroptosis.…”

Section: Factors Affecting Rt-induced Pyroptosismentioning

confidence: 99%

Pyroptotic cell death: an emerging therapeutic opportunity for radiotherapy

Li,

Yang,

Zhang

et al. 2024

Cell Death Discov.

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

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“…Wang et al [ 365 ] indicated that esculetin is safe and reliable, is easy to be absorbed by the body, and can be synthesized in a variety of ways. Esculetin inhibits the pyroptosis of microvascular endothelial cells through the NF-KB/NLFP3 signaling pathway and is expected to be conducive in treating pyroptosis-related diseases [ 366 ]. Esculetin directly binds to hnRNPA1 and decreases the concentration of hnRNPA1 in endometrial cancer cells, and it downregulates the levels of BCL-XL and XIAP expression, resulting in apoptosis and an arrest in proliferation [ 367 ].…”

Section: The Health Benefits Of Coumarins (Umbelliferone Esculetin Sc...mentioning

confidence: 99%

Therapeutic Potential of Phenolic Compounds in Medicinal Plants—Natural Health Products for Human Health

2023

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Phenolic compounds and flavonoids are potential substitutes for bioactive agents in pharmaceutical and medicinal sections to promote human health and prevent and cure different diseases. The most common flavonoids found in nature are anthocyanins, flavones, flavanones, flavonols, flavanonols, isoflavones, and other sub-classes. The impacts of plant flavonoids and other phenolics on human health promoting and diseases curing and preventing are antioxidant effects, antibacterial impacts, cardioprotective effects, anticancer impacts, immune system promoting, anti-inflammatory effects, and skin protective effects from UV radiation. This work aims to provide an overview of phenolic compounds and flavonoids as potential and important sources of pharmaceutical and medical application according to recently published studies, as well as some interesting directions for future research. The keyword searches for flavonoids, phenolics, isoflavones, tannins, coumarins, lignans, quinones, xanthones, curcuminoids, stilbenes, cucurmin, phenylethanoids, and secoiridoids medicinal plant were performed by using Web of Science, Scopus, Google scholar, and PubMed. Phenolic acids contain a carboxylic acid group in addition to the basic phenolic structure and are mainly divided into hydroxybenzoic and hydroxycinnamic acids. Hydroxybenzoic acids are based on a C6-C1 skeleton and are often found bound to small organic acids, glycosyl moieties, or cell structural components. Common hydroxybenzoic acids include gallic, syringic, protocatechuic, p-hydroxybenzoic, vanillic, gentistic, and salicylic acids. Hydroxycinnamic acids are based on a C6-C3 skeleton and are also often bound to other molecules such as quinic acid and glucose. The main hydroxycinnamic acids are caffeic, p-coumaric, ferulic, and sinapic acids.

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Esculetin inhibits the pyroptosis of microvascular endothelial cells through NF-κB /NLRP3 signaling pathway

Cited by 5 publications

References 22 publications

Inhibitory Effects of Esculetin on Liver Cancer Through Triggering NCOA4 Pathway-Mediation Ferritinophagy in vivo and in vitro

Inhibitory Effects of Esculetin on Liver Cancer Through Triggering NCOA4 Pathway-Mediation Ferritinophagy in vivo and in vitro

Pyroptotic cell death: an emerging therapeutic opportunity for radiotherapy

Therapeutic Potential of Phenolic Compounds in Medicinal Plants—Natural Health Products for Human Health

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