Cardamonin: A new player to fight cancer via multiple cancer signaling pathways

Life Sciences, Journal Year: 2020, Volume and Issue: 250, P. 117591 - 117591

Published: March 26, 2020

Language: Английский

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Curcumol inhibits ferritinophagy to restrain hepatocyte senescence through YAP/NCOA4 in non‐alcoholic fatty liver disease

Cell Proliferation, Journal Year: 2021, Volume and Issue: 54(9)

Published: Aug. 3, 2021

Abstract Objectives In recent years, cellular senescence has attracted a lot of interest in researchers due to its involvement non‐alcoholic fatty liver disease (NAFLD). However, the mechanism is not clear. The purpose this study was investigate effect curcumol on hepatocyte NAFLD and molecular mechanisms implicated. Materials methods LVG Golden Syrian hamsters, C57BL/6J mice human cell line LO2 were used. Cellular assessed by analyses marker SA‐β‐gal, p16 p21, H3K9me3, γ‐H2AX telomerase activity. Results results showed that could inhibit both vivo vitro models, might be related regulation ferritinophagy subsequent alleviation iron overload. Moreover, overexpression nuclear receptor coactivator 4 (NCOA4) weakened ferritinophagy‐mediated overload senescence. Furthermore, we demonstrated reduced expression NCOA4 Yes‐associated protein (YAP). addition, depression YAP impair Conclusion Our clarified inhibition through YAP/NCOA4 NAFLD. These findings provided promising option regulate target for treatment

Language: Английский

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Potential roles and molecular mechanisms of bioactive ingredients in Curcumae Rhizoma against breast cancer

Phytomedicine, Journal Year: 2023, Volume and Issue: 114, P. 154810 - 154810

Published: April 6, 2023

Language: Английский

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Curcumol: a review of its pharmacology, pharmacokinetics, drug delivery systems, structure–activity relationships, and potential applications

Inflammopharmacology, Journal Year: 2024, Volume and Issue: 32(3), P. 1659 - 1704

Published: March 23, 2024

Language: Английский

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Reversal of sorafenib resistance in hepatocellular carcinoma by curcumol: insights from network pharmacology, molecular docking, and experimental validation

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 2, 2025

Background Curcumol, a bioactive sesquiterpenoid extracted from traditional Chinese medicine (TCM), has demonstrated potential in overcoming tumor drug resistance. However, its mechanisms reversing resistance, particularly hepatocellular carcinoma (HCC) resistant to sorafenib, are not yet fully elucidated. This study aims explore the molecular by which curcumol reverses sorafenib resistance HCC using combination of network pharmacology, docking, and vivo vitro experiments. Methods We identified targets genes associated with sorafenib-resistant HCC, resulting set overlapping targets. These intersection underwent enrichment analysis DAVID, protein-protein interaction (PPI) was constructed via STRING database Cytoscape. Molecular docking confirmed binding core In assays, including CCK-8, colony formation assay, apoptosis detection, wound healing, Transwell evaluated curcumol’s effects on cells. Western blotting assessed impact PI3K/AKT JAK/STAT3 signaling pathways. Additionally, xenograft mouse model established observe efficacy combined sorafenib. Results 117 for HCC. Among them, five targets—ALB, STAT3, HSP90AA1, HSP90AB1, SRC—showed strong affinity curcumol. KEGG pathway intersecting highlighted significant involvement PI3K/AKT, JAK/STAT3, Ras, Rap1, HIF-1, FoxO, mTOR experiments revealed that significantly enhanced sensitivity cells inhibiting cell proliferation, invasion, migration while promoting apoptosis. studies further effectively inhibited growth models. Conclusion provides compelling evidence can reverse modulating multiple pathways, Our findings suggest holds promise as novel therapeutic agent offering new avenue clinical intervention.

Language: Английский

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Curcumol inhibits the expression of programmed cell death-ligand 1 through crosstalk between hypoxia-inducible factor-1α and STAT3 (T705) signaling pathways in hepatic cancer

Journal of Ethnopharmacology, Journal Year: 2020, Volume and Issue: 257, P. 112835 - 112835

Published: April 9, 2020

Language: Английский

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Curcumol Overcomes TRAIL Resistance of Non‐Small Cell Lung Cancer by Targeting NRH:Quinone Oxidoreductase 2 (NQO2)

Advanced Science, Journal Year: 2020, Volume and Issue: 7(22)

Published: Oct. 15, 2020

Abstract Resistance to tumor‐necrosis‐factor‐related apoptosis‐inducing ligand (TRAIL) of cancer cell remains a key obstacle for clinical therapies. To overcome TRAIL resistance, this study identifies curcumol as novel safe sensitizer from food‐source compound library, which exhibits synergistic lethal effects in combination with on non‐small lung (NSCLC). SILAC‐based cellular thermal shift profiling NRH:quinone oxidoreductase 2 (NQO2) the target curcumol. Mechanistically, directly targets NQO2 cause reactive oxygen species (ROS) generation, triggers endoplasmic reticulum (ER) stress‐C/EBP homologous protein (CHOP) death receptor (DR5) signaling, sensitizing NSCLC TRAIL‐induced apoptosis. Molecular docking analysis and surface plasmon resonance assay demonstrate that Phe178 is critical site binding. Mutation completely abolishes function augments sensitization. This characterizes functional role resistance by targeting NQO2, highlighting potential using an inhibitor treatment TRAIL‐resistant cancers.

Language: Английский

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Curcumol Suppresses CCF-Mediated Hepatocyte Senescence Through Blocking LC3B–Lamin B1 Interaction in Alcoholic Fatty Liver Disease

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: June 28, 2022

Recent studies indicated that hepatocyte senescence plays an important role in the development of alcoholic fatty liver disease (AFLD), suggesting inhibition might be a potential strategy for AFLD treatment. The present study investigated effect curcumol, component from root Rhizoma Curcumae, on and underlying mechanisms implicated. results showed curcumol was able to reduce lipid deposition injury livers ethanol liquid diet-fed mice ethanol-treated LO2 cells. Both vivo vitro supplementation with effectively alleviated ethanol-induced cellular as manifested by decrease senescence-associated β-galactosidase (SA-β-gal) activity, downregulated expression senescence-related markers p16 p21, dysfunction telomere telomerase system. Consistently, treatment led marked suppression formation cytoplasmic chromatin fragments (CCF) subsequent activation cGAS-STING, resulting significant reduction secretory phenotype (SASP)-related inflammatory factors' secretion. Further curcumol's CCF derived blocking interaction LC3B lamin B1 maintaining nuclear membrane integrity. Taken together, these capable ameliorating through senescence, which attributed its inactivation CCF-cGAS-STING pathway. These findings suggest promising use AFLD.

Language: Английский

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Curcumol alleviates liver fibrosis by inducing endoplasmic reticulum stress-mediated necroptosis of hepatic stellate cells through Sirt1/NICD pathway

PeerJ, Journal Year: 2022, Volume and Issue: 10, P. e13376 - e13376

Published: May 12, 2022

Liver fibrosis is a repair response process after chronic liver injury. During this process, activated hepatic stellate cells (HSCs) will migrate to the injury site and secrete extracellular matrix (ECM) produce fibrous scars. Clearing HSCs may be major strategy for treatment of fibrosis. Curcumol isolated from plants genus Curcuma can effectively induce apoptosis many cancer cells, but whether it clear remains clarified. In present study, we found that effect curcumol in treating was by inducing necroptosis HSCs. Receptor-interacting protein kinase 3 (RIP3) silencing could impair induced curcumol. Interestingly, endoplasmic reticulum (ER) stress-induced cellular dysfunction associated with curcumol-induced cell death. The ER stress inhibitor 4-PBA prevented necroptosis. We proved regulated via Sirtuin-1(Sirt1)/Notch signaling pathway. Sirt1-mediated deacetylation intracellular domain Notch (NICD) led degradation NICD, thereby inhibiting signalling pathway alleviate Specific knockdown Sirt1 male ICR mice further exacerbated CCl4-induced Overall, our study elucidates anti-fibrotic reveals underlying mechanism between

Language: Английский

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Investigation on the mechanisms by which the herbal remedies induce anti-prostate cancer activity: uncovering the most practical natural compound

Journal of Biomolecular Structure and Dynamics, Journal Year: 2023, Volume and Issue: 42(7), P. 3349 - 3362

Published: May 17, 2023

Prostate cancer (PCa) is one of the most reported cancers among men worldwide. Targeting essential proteins associated with PCa could be a promising method for treatment. Traditional and herbal remedies (HRs) are practical approaches Here, enzymes were determined based on information obtained from DisGeNET database. The gene-disease association (GDA) score greater than 0.7 genes that have disease specificity index (DSI) = 1 selected as target proteins. 28 HRs anti-PCa activity traditional treatment chosen potential bioactive compounds. More 500 compound-protein complexes screened to find top-ranked bioactives. results further evaluated using molecular dynamics (MD) simulation binding free energy calculations. outcomes revealed procyanidin B2 3,3′‐di‐O‐gallate (B2G2), active ingredient grape seed extract (GSE), can act an agonist PTEN. PTEN has key role in suppressing cells by applying phosphatase inhibiting cell proliferation. B2G2 exhibited considerable affinity (11.643 kcal/mol). MD indicated stabilize residues domain increase its activity. Based results, GSE, B2G2, play effectively useful nutrition used men's diets inhibit their bodies.Communicated Ramaswamy H. Sarma

Language: Английский

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