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

Selected Flavonols Targeting Cell Death Pathways in Cancer Therapy: The Latest Achievements in Research on Apoptosis, Autophagy, Necroptosis, Pyroptosis, Ferroptosis, and Cuproptosis DOI Open Access
Dominika Wendlocha, Robert Kubina, Kamil Krzykawski

et al.

Nutrients, Journal Year: 2024, Volume and Issue: 16(8), P. 1201 - 1201

Published: April 18, 2024

The complex and multi-stage processes of carcinogenesis are accompanied by a number phenomena related to the potential involvement various chemopreventive factors, which include, among others, compounds natural origin such as flavonols. use flavonols is not only promising but also recognized strategy for cancer treatment. impact on arises from their ability act antioxidants, impede proliferation, promote cell death, inhibit angiogenesis, regulate immune system through in diverse forms cellular death. So far, molecular mechanisms underlying regulation apoptosis, autophagy, necroptosis, pyroptosis, ferroptosis, cuproptosis occurring with participation have remained incompletely elucidated, results studies carried out so far ambiguous. For this reason, one therapeutic goals initiate death altered cells quercetin, kaempferol, myricetin, isorhamnetin, galangin, fisetin, morin. This article offers an extensive overview recent research these compounds, focusing particularly role combating elucidating governing cuproptosis. Assessment anticancer effects therapy targeting types pathways may prove useful developing new regimens counteracting resistance previously used treatments.

Language: Английский

Citations

15
Therapeutic potentials and targeting strategies of quercetin on cancer cells: Challenges and future prospects DOI

Udaya Rajesh R,

D. Sangeetha

Phytomedicine, Journal Year: 2024, Volume and Issue: 133, P. 155902 - 155902

Published: July 22, 2024

Language: Английский

Citations

10
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
CDK4/6 inhibitors upregulate cIAP1/2, and Smac mimetic LCL161 enhances their antitumor effects in cholangiocarcinoma cells DOI Creative Commons

Pimchanok Menapree,

Nattaya Duangthim,

Apiwit Sae-Fung

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 25, 2025

Cholangiocarcinoma (CCA) is a highly aggressive bile duct cancer with poor prognosis and high mortality rates, primarily due to the lack of early diagnosis effective treatments. We have shown that cyclin D CDK4/6, key regulators cell cycle progression, are expressed in CCA patients. Moreover, levels D, CDK4, CDK6 associated shorter survival patients, suggesting CDK4/6 might be potential targets for therapy. However, we demonstrated inhibitor palbociclib monotherapy less cells. identified Cellular Inhibitor Apoptosis Proteins 1 2 (cIAP1/2), NF-κB target genes their expression as response. showed palbociclib, inhibitor, increases phosphorylated p65 its nuclear translocation, resulting cIAP1/2 upregulation Therefore, hypothesized combination antagonist enhance Interestingly, combined treatment Smac mimetic LCL161, antagonist, synergistically inhibits proliferation induces death both 2D monolayer 3D spheroid cultures. further this has effect on non-tumor cholangiocytes human peripheral blood mononuclear cells (PBMCs). Our findings demonstrate first time mimetics inhibitors promising novel targeted therapy

Language: Английский

Citations

0
Antioxidant Activity of Quercetin-Containing Liposomes-in-Gel and Its Effect on Prevention and Treatment of Cutaneous Eczema DOI Creative Commons
Chang Liu,

Xiaoman Cheng,

Yifang Wu

et al.

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(8), P. 1184 - 1184

Published: Aug. 21, 2023

Cutaneous eczema is a kind of skin disease characterized by inflammation. The main manifestations are various types dermatitis, eczema, and urticaria. There usually complications such as erythema, blisters, epidermal peeling. quercetin might have therapeutic effect on cutaneous due to its favorable antioxidant activity anti-inflammatory effects. Currently, there few studies transdermal administration drugs for the treatment eczema. aim this study was prepare quercetin-containing liposomes-in-gel (QU-LG), properties were evaluated, it used in mice suffering from dermal see if had preventive effects an attempt make new option QU-LG prepared injection method form liposomes (QU-L) evenly dispersed natural dissolution carboxymethylcellulose sodium (1%, CMC-Na). release across dialysis membranes up 30% clearance 1,1-diphenyl-2-picrylhydrazyl (DPPH) 65.16 ± 3.513%. In anti-oxidation assay inhibited malondialdehyde (MDA) production liver better than commercially available drug dexamethasone acetate cream. Compared with untreated mice, treated showed statistically significant reduction dermatopathologic symptoms. results suggested that good vivo vitro could be prevention

Language: Английский

Citations

10
Cytotoxicity, Proapoptotic Activity and Drug-like Potential of Quercetin and Kaempferol in Glioblastoma Cells: Preclinical Insights DOI Open Access
Magdalena Kusaczuk, Elena Tovar-Ambel, Paola Martín-Cabrera

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(19), P. 10740 - 10740

Published: Oct. 5, 2024

Despite the increasing understanding of pathogenesis glioblastoma (GBM), treatment options for this tumor remain limited. Recently, therapeutic potential natural compounds has attracted great interest. Thus, dietary flavonoids quercetin (QCT) and kaempferol (KMF) were investigated as cytostatic agents in GBM. Moreover, physicochemical properties QCT KMF, determining their bioavailability efficiency, evaluated. We proved that both polyphenols significantly reduced viability GBM cells. also demonstrated KMF evoked cytotoxic effect T98G cells via induction apoptotic cell death shown by increased activity caspase 3/7 9 together with an overexpression cleaved form PARP. Apoptosis was additionally accompanied activation stress responses QCT- KMF-treated Both caused oxidative endoplasmic reticulum (ER) stress, generation reactive oxygen species (ROS), deregulated expressions superoxide dismutases (SOD2

Language: Английский

Citations

3
Targeting programmed cell death via active ingredients from natural plants: a promising approach to cancer therapy DOI Creative Commons
Qian Li, Yan Tong, Jianxiang Chen

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 1, 2024

Cancer is a serious public health problem in humans, and prevention control strategies are still necessary. Therefore, the development of new therapeutic drugs urgently needed. Targeting programmed cell death, particularly via induction cancer apoptosis, one treatment approaches employed. Recently, an increasing number studies have shown that compounds from natural plants can target death kill cells, laying groundwork for use future anticancer treatments. In this review, we focus on latest research progress role mechanism plant active ingredients different forms such as autophagy, necroptosis, ferroptosis, pyroptosis, to provide strong theoretical basis clinical antitumor drugs.

Language: Английский

Citations

1
Kaempferol inhibits the proliferation and migration of Epstein-Barr virus-positive diffuse large B-cell lymphoma cells DOI Creative Commons

Suli Lu,

Zhen Wang,

Dae-jung Yang

et al.

Tropical Journal of Pharmaceutical Research, Journal Year: 2024, Volume and Issue: 23(2), P. 257 - 262

Published: March 12, 2024

Purpose: To assess the effect of kaempferol on growth, apoptosis, and motility Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) cells, to elucidate its mechanism action. Methods: Human DLBCL cells were used generate EBV-positive (EBV +) cell line Pfeiffer. CCK-8, colony formation, flow cytometry (FCM), immunoblot assays employed determine effects growth apoptosis EBV + cells. Cell was evaluated by Transwell assays. Immunoblot assay further conducted unravel Results: Kaempferol inhibited It also enhanced but Furthermore, PI3K/AKT axis, thereby suppressing DLBCL. Conclusion: inhibits via axis. is therefore a potential drug for treatment

Language: Английский

Citations

0
Anti-Inflammatory and Cancer-Preventive Potential of Chamomile (Matricaria chamomilla L.): A Comprehensive In Silico and In Vitro Study DOI Creative Commons
Assia I. Drif, Rümeysa Yücer, Roxana Damiescu

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(7), P. 1484 - 1484

Published: July 5, 2024

Background and aim: Chamomile tea, renowned for its exquisite taste, has been appreciated centuries not only flavor but also myriad health benefits. In this study, we investigated the preventive potential of chamomile (Matricaria chamomilla L.) towards cancer by focusing on anti-inflammatory activity. Methods results: A virtual drug screening 212 phytochemicals from revealed β-amyrin, β-eudesmol, β-sitosterol, apigenin, daucosterol, myricetin as potent NF-κB inhibitors. The in silico results were verified through microscale thermophoresis, reporter cell line experiments, flow cytometric determination reactive oxygen species mitochondrial membrane potential. An oncobiogram generated comparison 91 anticancer agents with known modes action using NCI tumor panel significant relationships cytotoxic compounds, lupeol, quercetin to microtubule This hypothesis was confocal microscopy α-tubulin-GFP-transfected U2OS cells molecular docking lupeol tubulins. Both compounds induced G2/M cycle arrest necrosis rather than apoptosis. Interestingly, involved major mechanisms resistance established drugs (ABC transporters, TP53, or EGFR). Performing hierarchical cluster analyses proteomic expression data identified two sets 40 proteins determining sensitivity quercetin, further pointing multi-specific nature compounds. Furthermore, β-amyrin inhibited mRNA proinflammatory cytokines IL-1β IL6 (HEK-Blue Null1). Moreover, Kaplan–Meier-based survival target protein these performed mining TCGA-based KM-Plotter repository 7489 patients. Renal clear carcinomas (grade 3, low mutational rate, neoantigen load) significantly associated shorter patients, indicating that subgroups tumors might benefit inhibition Conclusion: study chamomile, positioning it a promising agent against inflammation cancer. Further research clinical studies are recommended.

Language: Английский

Citations

0
Quercetin: A Flavonoid with Diverse Chemo Preventive Properties against Cancer DOI
Mohammed I. Rushdi

IntechOpen eBooks, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 4, 2024

Quercetin, an exceptional and extraordinary flavonoid possessing bioactive properties, presents a plethora of benefits for the promotion good health. The anti-tumor characteristics quercetin have been well-documented in various vitro vivo investigations, encompassing wide range cell lines animal models. through activation caspase-3 inhibition phosphorylation Akt, mTOR, ERK, as well reduction β-catenin stabilization HIF-1α, augments apoptosis autophagy cancer. Additionally, curbs cancer metastasis by decreasing MMP VEGF secretion. Significantly, potent cytotoxicity against cells is accompanied minimal or no adverse effects harm to healthy cells.

Language: Английский

Citations

0