Jianpi Yangzheng Xiaozheng granule induced ferroptosis to suppress gastric cancer progression through reprogramming lipid metabolism via SCD1/Wnt/β-catenin axis

Frontiers in Molecular Biosciences, Journal Year: 2025, Volume and Issue: 12

Published: Feb. 25, 2025

The incidence of Poorly cohesive carcinoma (PCC) has steadily risen in recent years, posing a significant clinical challenge. To reveal the anti-tumor effects Jianpi Yangzheng Xiaozheng granule (JPYZXZ) PCC, an initial investigation was performed using CCK-8, colony formation, scratch, and transwell assays. This followed by network pharmacology studies to gain deeper understanding JPYZXZ's impact on gastric cancer (GC). Then reactive oxygen species (ROS), Fe2+, malondialdehyde (MDA), glutathione (GSH), Oil Red O staining, BODIPY493/503, triglyceride (TG), cholesterol (TC) assay kits western blot (Wb) analysis were applied exam regulatory JPYZXZ ferroptosis lipid metabolism. Additionally, molecular docking Wb used further investigate mechanisms PCC. Finally, vivo animal conducted. results show that can inhibit proliferation migration PCC cell. It increases levels ROS, MDA, while declining content GSH, TC, TG, droplet accumulation within cellular compartments. indicates negatively regulate expression proteins, including peroxidase 4 (GPX4), cystine/glutamate antipoter SLC7A11 (xCT), fatty acid synthase (FASN), acetyl coenzyme A carboxylase 1 (ACC1). Furthermore, ferrostatin-1 (fer-1) is able reverse aforementioned markers Molecular analyses exhibits favorable binding affinity towards Stearoyl-Coenzyme desaturase (SCD1). Mechanism demonstrate capable down-regulating expressions proteins like SCD1, β-catenin, GPX4, xCT, which analogous SCD1 knockdown application inhibitor A939572. Nevertheless, when knocked down, unable downregulate these proteins. Animal have corroborated vitro tumor-inhibiting JPYZXZ. Therefore, this study offers first evidence inhibits progression orchestrating altering metabolism, mediated SCD1/Wnt/β-catenin pathway.

Language: Английский

Bee Pollen Potential to Modulate Ferroptosis: Phytochemical Insights for Age-Related Diseases

Antioxidants, Journal Year: 2025, Volume and Issue: 14(3), P. 265 - 265

Published: Feb. 25, 2025

Bee pollen (BP) is one of the richest known natural resources micronutrients and bioactive phytochemicals. Some captivating bioactivities BP compounds, although being largely investigated for latter as individual molecules, remain very scarcely or completely uninvestigated in bee a whole product. Among most intriguing these bioactivities, we identified ferroptosis major one. Ferroptosis, recently discovered form cell death (connecting oxidative stress inflammation), complex pathophysiological process crucial perplexing events current challenging human diseases such cancer, neurodegeneration, general aging diseases. Many compounds were found to intricately modulate depending on cellular context by inducing this mechanism malignant cells preventing it non-malignant cells. Since research both fields, i.e., ferroptosis, still recent, deemed necessary undertake review figure out extent potential modulating mechanisms. Our proved that wide range (polyphenols, phenolamides, carotenoids, vitamins, minerals, others) substantially diverse Accordingly, phytochemicals nutrients showed interesting preclinical studies lead ferroptosis-mediated outcomes important processes, including many aging-related disorders. One paramount challenges be resolved determine how different act biological contexts, either through synergistic antagonistic behaviors. We hope our work constitutes valuable incentive future investigations promising relevant avenue.

Language: Английский

KLX ameliorates liver cancer progression by mediating ZBP1 transcription and ubiquitination and increasing ZBP1-induced PANoptosis

Acta Pharmacologica Sinica, Journal Year: 2025, Volume and Issue: unknown

Published: March 27, 2025

Abstract Liver cancer is a highly aggressive malignancy with poor survival rates. Current treatments, including liver transplantation, immunotherapy, and gene therapy, are often limited by late-stage diagnosis significant side effects, highlighting the urgent need for novel therapeutic agents. In this study, we evaluated potential of Kanglexin (KLX), anthraquinone derivative, in treatment cancer. vitro, KLX inhibited proliferation migration HepG2 Hep3B cells dose-dependent manner. Mechanistically, upregulated Z-DNA binding protein 1 (ZBP1) expression, inducing PANoptosis directly to ZBP1, altering its conformation, reducing affinity E3 ubiquitin ligase ring finger 180 (RNF180). This interaction decreased ZBP1 ubiquitination, thereby increasing stability. Additionally, expression transcription factor homeobox D10 (HOXD10), which further increased expression. Elevated levels significantly suppressed cell migration, whereas inhibitory effects were reversed upon knockdown. xenograft model, tumor growth lower toxicity than oxaliplatin (OXA). conclusion, promoted upregulating preventing degradation, inhibiting progression migration. These findings suggest that promising agent

Language: Английский