2‐Undecanone induces ferroptosis via the STAT3/GPX4 pathway to enhance sensitivity of renal cell carcinoma to sunitinib

BioFactors, Год журнала: 2025, Номер 51(2)

Опубликована: Март 1, 2025

Abstract The development of resistance significantly reduces the efficacy targeted therapies, such as sunitinib, in renal cell carcinoma (RCC) patients, emphasizing need for novel therapeutic agents. Natural products, known their diverse chemical structures and mechanisms action, offer promising anti‐tumor potential with favorable safety profiles lower toxicity compared to synthetic drugs. 2‐Undecanone, a natural compound extracted from Houttuynia cordata Thunb., has demonstrated effects, but its specific role RCC treatment remains unclear. In this study, we integrated network pharmacology vitro experiments explore underlying 2‐Undecanone's effects on RCC. Our results reveal that 2‐Undecanone effectively inhibits viability, proliferation, migration. Mechanistically, discovered induces ferroptosis cells by promoting reactive oxygen species (ROS) generation, intracellular Fe 2+ accumulation, glutathione (GSH) production, lipid peroxidation, modulation STAT3/GPX4 signaling pathway. Furthermore, lowers IC50 value sunitinib cells, enhancing sensitivity therapy. Additionally, potentiates sunitinib‐induced ferroptosis. summary, our research reveals enhances through targeting pathway, providing new insights into strategies

Язык: Английский

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Influence of gut microbial metabolites on tumor immunotherapy: mechanisms and potential natural products

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Фев. 24, 2025

In recent years, tumor immunotherapy has made significant breakthroughs in the treatment of malignant tumors. However, individual differences efficacy have been observed clinical practice. There is increasing evidence that gut microbial metabolites influence distal via gut-liver axis, gut-brain axis and gut-breast a process may involve modulating expression immune cells cytokines microenvironment (TME). this review, we systematically explore relationship between immunotherapy, examine corresponding natural products their mechanisms action. The in-depth exploration research area will provide new ideas strategies to enhance mitigate adverse effects.

Язык: Английский

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Development and Optimization of Curcumin-Loaded Citric Acid Functionalized Multi-Walled Carbon Nanotubes for Enhanced Breast Cancer Treatment Using Design of Experiment

Journal of Pharmaceutical Innovation, Год журнала: 2025, Номер 20(2)

Опубликована: Фев. 28, 2025

Язык: Английский

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Network pharmacology and in vitro experiments based strategy to explore the effects of Jujuboside A on the proliferation and migration ability of glioma cells

Brain Research, Год журнала: 2025, Номер unknown, С. 149570 - 149570

Опубликована: Март 1, 2025

Язык: Английский

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Design, synthesis and biological activity of novel Xuetongsu derivatives as potential anticancer agents by inducing apoptosis

Journal of Enzyme Inhibition and Medicinal Chemistry, Год журнала: 2025, Номер 40(1)

Опубликована: Апрель 8, 2025

Xuetongsu (XTS, Schisanlactone E) is one of the main active compounds and considered as star molecule isolated from Kadsura heteroclita (Roxb.) Craib. In order to improve XTS anti-tumour bioactivities, a series novel derivatives were designed synthesised by introducing an amide bond at parent. Anti-proliferative assays on four different human tumour cell lines (BGC-823, HepG-2, HCT-116, MCF-7) showed that activities most increased greatly compared parent XTS, especially, A-7, A-14, A-18 exhibited multiple effects. Among them, compound A-7 has best biological with IC50 values ranging 13.86 20.71 μM, which could significantly increase fraction apoptotic cells according flow cytometry experience. Further study demonstrated induce apoptosis HepG-2 through influencing key related proteins, such Bcl-2, Bax, cleaved Caspase-3.

Язык: Английский

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Natural Compounds in Cancer Therapy: Revealing the Role of Flavonoids in Renal Cell Carcinoma Treatment

Biomolecules, Год журнала: 2025, Номер 15(5), С. 620 - 620

Опубликована: Апрель 25, 2025

Renal cell carcinoma (RCC) is the most lethal malignancy of urinary system, with limited treatment options due to drug resistance and adverse effects associated current therapies. This review aims systematically examine therapeutic potential flavonoids, which are natural polyphenolic compounds possessing anti-inflammatory, antioxidant, anticancer properties, in context RCC treatment. We summarize activities 26 classified into six subclasses, explore their mechanisms action, including inhibition tumor proliferation, migration, invasion, as well induction apoptosis, autophagy, ferroptosis. Particular attention paid modulation key signaling pathways such JAK/STAT3, PI3K/Akt/mTOR, miRNA-related axes, miR-21/YAP1 miR-324-3p/GPX4, providing a molecular basis for anti-RCC activity. also address several pharmacological challenges that limit clinical application poor bioavailability, metabolic instability, toxicity. Emerging solutions novel flavonoid derivatives, advanced delivery systems, rational combination therapy strategies discussed. Current evidence, phase II trial flavopiridol RCC, highlights but need further validation. In conclusion, flavonoids offer promising approach improving Future research should focus on optimizing efficacy ensuring safe translation, goal achieving personalized minimally invasive cancer

Язык: Английский

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Green tea catechins: protectors or threats to DNA? A review of their antigenotoxic and genotoxic effects

Archives of Toxicology, Год журнала: 2025, Номер unknown

Опубликована: Май 13, 2025

Язык: Английский

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A Natural Alkaloid, 6-Hydroxymethyldihydronitidine, Suppresses Tumor Progression by Co-Regulating Apoptosis, Ferroptosis, and FAK Pathways

Biomolecules, Год журнала: 2025, Номер 15(6), С. 814 - 814

Опубликована: Июнь 4, 2025

Cancer treatment remains a formidable challenge globally. Natural products, particularly natural alkaloids, have emerged as significant resources for the development of novel anti-tumor drugs due to their structural diversity and unique biological activities. Our team previously isolated an alkaloid, 6-hydroxymethyldihydrochelerythrine (6-HMDN), from Zanthoxylum ailanthoides. Subsequent in vitro vivo activity screenings, utilizing cell-based assays zebrafish xenograft model, revealed that 6-HMDN significantly inhibited proliferation HepG2 MCF7 cells effectively suppressed cell migration. Mechanistic studies indicated induced tumor apoptosis by modulating Bcl-2/Bax protein balance activating caspase cascade. Furthermore, augmented intracellular reactive oxygen species (ROS) levels, thereby promoting ferroptosis, evidenced lipid ROS accumulation glutathione (GSH) depletion. Additionally, attenuated focal adhesion kinase (FAK) phosphorylation, leading inhibition In experiments further substantiated capacity suppress metastasis. These findings demonstrate exhibits potent activity, exerting its effects through multiple mechanisms involving regulation apoptosis, FAK signaling pathway. Therefore, may be considered promising candidate drug development.

Язык: Английский

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Determination of beneficial effects of cuminaldehyde on hyperglycemia associated kidney malfunctions

Naunyn-Schmiedeberg s Archives of Pharmacology, Год журнала: 2024, Номер unknown

Опубликована: Сен. 28, 2024

Язык: Английский

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Revealing the Mechanism of Esculin in Treating Renal Cell Carcinoma Based on Network Pharmacology and Experimental Validation

Biomolecules, Год журнала: 2024, Номер 14(8), С. 1043 - 1043

Опубликована: Авг. 22, 2024

Purpose: This study aims to explore the potential mechanisms of esculin in treatment renal cell carcinoma (RCC). Methods: We employed network pharmacology predict and targets RCC. Molecular docking techniques were then validate predicted targets. Additionally, a series vitro experiments conducted verify anticancer effects on RCC cells, including CCK-8 assay, EdU wound healing apoptosis Western blot. Results: Network molecular results identified GAPDH, TNF, GSK3B, CCND1, MCL1, IL2, CDK2 as core GO KEGG analyses suggested that may influence apoptotic processes target PI3K/Akt pathway Furthermore, assay demonstrated inhibited viability. Microscopic observations revealed following treatment, there was an increase crumpling, reduction density, accumulation floating dead cells. with increasing concentrations, proportion EdU-positive cells decreased, closure ratio PI-positive increased, expression levels BAX cleaved-caspase-3 proteins level Bcl2 protein decreased. These findings inhibits proliferation migration while promoting apoptosis. Moreover, found GAPDH inhibit pathway. Conclusions: is first elucidate therapeutic The provide evidence supporting clinical application introduce promising new candidate for treatment.

Язык: Английский

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