Jianpi Yangzheng Xiaozheng granule induced ferroptosis to suppress gastric cancer progression through reprogramming lipid metabolism via SCD1/Wnt/β-catenin axis DOI Creative Commons
Xiangyang Wang, Jiachen Li, Rong Qin

et al.

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

Ferroptosis and Its Role in Chronic Diseases DOI Creative Commons
Wenli Hu, Kehong Liang, Hong Zhu

et al.

Cells, Journal Year: 2022, Volume and Issue: 11(13), P. 2040 - 2040

Published: June 27, 2022

Ferroptosis, which has been widely associated with many diseases, is an iron-dependent regulated cell death characterized by intracellular lipid peroxide accumulation. It exhibits morphological, biochemical, and genetic characteristics that are unique in comparison to other types of death. The course ferroptosis can be accurately the metabolism iron, lipids, amino acids, various signal pathways. In this review, we summarize basic ferroptosis, its regulation, as well relationship between chronic diseases such cancer, nervous system metabolic inflammatory bowel diseases. Finally, describe regulatory effects food-borne active ingredients on ferroptosis.

Language: Английский

Citations

62
The Impact of Oxidative Stress and AKT Pathway on Cancer Cell Functions and Its Application to Natural Products DOI Creative Commons
Jun‐Ping Shiau,

Ya-Ting Chuang,

Jen‐Yang Tang

et al.

Antioxidants, Journal Year: 2022, Volume and Issue: 11(9), P. 1845 - 1845

Published: Sept. 19, 2022

Oxidative stress and AKT serine-threonine kinase (AKT) are responsible for regulating several cell functions of cancer cells. Several natural products modulate both oxidative anticancer effects. However, the impact product-modulating on lacks systemic understanding. Notably, contribution by downstream effectors is not yet well integrated. This review explores role pathway (AKT/AKT effectors) ten functions, including apoptosis, autophagy, endoplasmic reticulum stress, mitochondrial morphogenesis, ferroptosis, necroptosis, DNA damage response, senescence, migration, cell-cycle progression. The connected to these through function mediators. Moreover, related Based this rationale, with modulating abilities exhibit potential regulate but some were rarely reported, particularly effectors. sheds light understanding roles in providing future directions treatment.

Language: Английский

Citations

41
Emerging significance and therapeutic targets of ferroptosis: a potential avenue for human kidney diseases DOI Creative Commons
Jinghan Li,

Sujuan Zheng,

Yumei Fan

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(9)

Published: Sept. 22, 2023

Abstract Kidney diseases remain one of the leading causes human death and have placed a heavy burden on medical system. Regulated cell contributes to pathology plethora renal diseases. Recently, with in-depth studies into kidney death, new iron-dependent modality, known as ferroptosis, has been identified attracted considerable attention among researchers in pathogenesis therapeutics treat them. The majority suggest that ferroptosis plays an important role pathologies multiple diseases, such acute injury (AKI), chronic disease, carcinoma. In this review, we summarize recently regulatory molecular mechanisms discuss pathways action various describe protective effect inhibitors against especially AKI. By summarizing prominent roles different progress made studying provide directions strategies for future research summary, ferroptotic factors are potential targets therapeutic intervention alleviate targeting them may lead treatments patients

Language: Английский

Citations

28
Nobiletin in Cancer Therapy; Mechanisms and Therapy Perspectives DOI

Reza Moazamiyanfar,

Sepideh Rezaei,

Hasan Aliashrafzadeh

et al.

Current Pharmaceutical Design, Journal Year: 2023, Volume and Issue: 29(22), P. 1713 - 1728

Published: April 27, 2023

Cancer has remained to be one of the major challenges in medicine and regarded as second leading cause death worldwide. Different types cancer may resist anti-cancer drugs following certain mutations such those tumor suppressor genes, exhaustion immune system, overexpression drug resistance mediators, which increase required concentration anticancer so overcome resistance. Moreover, treatment with a high dose is highly associated severe normal tissue toxicity. Administration low-toxic agents long been an intriguing idea enhance suppression. Naturally occurring e.g., herb-derived molecules have shown dual effect on malignant cells. On hand, these induce cell cells, while other hand reduce Nobiletin, well-known polymethoxyflavones (PMFs), reportedly various beneficial effects suppression protection cells against different toxic agents. Our review aims explain main mechanisms underlying nobiletin inhibitor cancer. We reviewed caused by nobiletin, stimulation reactive oxygen species (ROS), modulation evasion mechanisms, targeting epigenetic modulators, among others; inhibitory affecting properties hypoxia, multidrug resistance, angiogenesis, epithelial-mesenchymal transition (EMT) fully investigated. Also, inhibition anti-apoptotic invasive induced will later discussed. In end, protective cells/tissue, clinical trial results, future perspectives are reviewed.

Language: Английский

Citations

22
Natural product-derived ferroptosis mediators DOI
Yili Chen,

Lin-An Xiong,

Lie‐Feng Ma

et al.

Phytochemistry, Journal Year: 2024, Volume and Issue: 219, P. 114002 - 114002

Published: Jan. 27, 2024

Language: Английский

Citations

12
Melanoma biology and treatment: a review of novel regulated cell death-based approaches DOI Creative Commons

Ming-yun Hsieh,

Sheng‐Kai Hsu,

Tzu‐Yu Liu

et al.

Cancer Cell International, Journal Year: 2024, Volume and Issue: 24(1)

Published: Feb. 9, 2024

Abstract The incidence of melanoma, the most lethal form skin cancer, has increased due to ultraviolet exposure. treatment advanced particularly metastatic cases, remains challenging with poor outcomes. Targeted therapies involving BRAF/MEK inhibitors and immunotherapy based on anti-PD1/anti-CTLA4 antibodies have achieved long-term survival rates approximately 50% for patients melanoma. However, therapy resistance inadequate response continue hinder further breakthroughs in treatments that increase rates. This review provides an introduction molecular-level pathogenesis melanoma offers overview current options their limitations. Cells can die by either accidental or regulated cell death (RCD). RCD is orderly controlled a variety macromolecules maintain stability internal environment. Since uncontrolled proliferation tumor cells requires evasion programs, inducing may be strategy. summarizes studies various types nonapoptotic RCDs, such as autophagy-dependent death, necroptosis, ferroptosis, pyroptosis, recently discovered cuproptosis, context relationships between these RCDs are examined, interplay targeted discussed. Given findings demonstrating different stimuli associated induction shows promise integral component strategies

Language: Английский

Citations

11
The Circadian Clock Component RORA Increases Immunosurveillance in Melanoma by Inhibiting PD-L1 Expression DOI Creative Commons
Dandan Liu, Benliang Wei, Long Liang

et al.

Cancer Research, Journal Year: 2024, Volume and Issue: 84(14), P. 2265 - 2281

Published: May 8, 2024

Circadian clock perturbation frequently occurs in cancer and facilitates tumor progression by regulating malignant growth shaping the immune microenvironment. Emerging evidence has indicated that genes are disrupted melanoma linked to escape. Herein, we found expression of retinoic acid receptor-related orphan receptor-α (RORA) is downregulated patients with higher RORA have a better prognosis after immunotherapy. Additionally, was significantly positively correlated T-cell infiltration recruitment. Overexpression or activation stimulated cytotoxic T-cell-mediated antitumor responses. bound CD274 promoter formed an inhibitory complex HDAC3 suppress PD-L1 expression. In contrast, DEAD-box helicase family member DDX3X competed for binding RORA, overexpression promoted release from suppressive thereby increased generate environment. The combination agonist anti-CTLA4 antibody synergistically immunity vivo. A score based on combined HDAC3, DDX3X, immunotherapy response patients. Together, this study elucidates mechanism component-regulated immunity, which will help inform use lead improved outcomes receiving therapeutic treatments. Significance: forms corepressor inhibit activate responses, indicating potential target predictive biomarker improve

Language: Английский

Citations

10
Nobiletin Ameliorates Aging of Chicken Ovarian Prehierarchical Follicles by Suppressing Oxidative Stress and Promoting Autophagy DOI Creative Commons

Jingchun Bai,

Xinyu Wang, Yiqiu Chen

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(5), P. 415 - 415

Published: Feb. 27, 2024

With the increase in age of laying chickens, aging follicles is accelerated, and reproductive ability decreased. Increased oxidative stress mitochondrial malfunction are indispensable causes ovarian aging. In this study, physiological condition prehierarchical small white (SWFs) was compared between D280 high-producing chickens D580 effect a plant-derived flavonoid nobiletin (Nob), natural antioxidant, on senescence SWFs granulosa cells (SWF-GCs) investigated. The results showed that Nob treatment activated cell autophagy by activating AMP-activated protein kinase (AMPK) Sirtuin-1 (SIRT1) pathways D-galactose (D-gal)-generated senescent SWF-GCs, restoring expression proliferation-related mRNAs proteins. addition, inflammation-related NF-κB significantly enhanced GCs were induced D-gal. supplementation increased antioxidant capacity decreased several genes associated with apoptosis. Furthermore, promoted activation PINK1 Parkin for mitophagy alleviated edema. Either AMPK inhibitor dorsomorphin (Compound C) or SIRT1 selisistat (EX-527) attenuated mitophagy. protective aging, GC proliferation, elimination beneficial impact energy regulation naturally ovaries diminished inhibition Nob-mediated autophagy. These data suggest increases mitophagy-related proteins (PINK1 Parkin) via AMPK/SIRT1 to prevent chickens.

Language: Английский

Citations

9
Perfluorooctanoic Acid Induces Ferroptosis in Hepatocytes via Oxidative Stress and AKT/GSK3β/β-Catenin Pathway Disruption DOI Creative Commons
Feng Yuan, Bin Lü,

Yongheng Huang

et al.

ACS Omega, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

Perfluorooctanoic acid (PFOA), a typical environmental contaminant, has been observed in tissue samples of various diseases, including liver cancer. PFOA can lead to hepatotoxicity, but the underlying molecular mechanism remains unclear. Our results showed that significantly inhibited HL-7702 (L02) and MIHA cell viability time- dose-dependent manner. Furthermore, could cause oxidative stress, mitochondrial injury, ferroptosis. In addition, upregulated levels malondialdehyde glutathione/oxidized glutathione downregulated expressions SLC7A11 GPX4, which refer phenotypes suppressed phosphorylation signaling cascades AKT/GSK3β/β-catenin, indicating signal pathway might be related order prove above hypothesis, Wnt activator chir99021 was used result revealed PFOA-induced inhibition p-AKT its downstream effectors p-GSK3β, SLC7A11, GPX4 counteracted. On other hand, inhibitor p-AKT, Ly294002, strengthened PFOA's regulatory actions on these factors. Overall, our suggest injury by inducing stress The effects are conferred through regulation AKT/GSK3β/β-catenin cascades.

Language: Английский

Citations

1
Yi-qi-hua-yu-jie-du decoction induces ferroptosis in cisplatin-resistant gastric cancer via the AKT/GSK3β/NRF2/GPX4 axis DOI
Wenjie Huang, Fang Wen, Peipei Yang

et al.

Phytomedicine, Journal Year: 2023, Volume and Issue: 123, P. 155220 - 155220

Published: Nov. 18, 2023

Language: Английский

Citations

21