Frontiers in Oncology
·
2021
·
IF 6.244
Yuan Yin,Ni Shuo,Zhuge Aoxiang,Li Bo,Li Lanjuan
Iron promotes the proliferation of cancer cells, but it also contributes to cell death. Here we explored whether iron could promote the Warburg effect of colorectal cancer (CRC) cells and suppress sensitivity to ferroptosis by inducing reactive oxygen species (ROS) and regulating nuclear factor erythroid 2-related factor 2 (NRF2). In this study, cell proliferation abilities were measured by CCK-8, EdU incorporation, and colony formation assays. Seahorse XF96 respirometry assays were used to detect the Warburg effect and the level of ROS was assess by DCFH-DA fluorescent probes. Results showed that iron exposure promoted the Warburg effect of CRC cells by inducing ROS and activating NRF2 both in vivo and in vitro. In addition, iron exposure also induced ferroptosis in CRC cells, but at the same time its inhibitory proteins SLC7A11 and GPX4 were also upregulated, indicating an enhanced resistance to ferroptosis. Our results revealed that iron can effectively promote tumorigenesis. Meanwhile, iron elimination or a low-iron diet might be valid therapeutic approaches for CRC.
研究领域:
肿瘤学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Food Production Processing and Nutrition
·
2026
·Vol. 8
·期 1
·72
·
IF 6.3
Niu Ruge,Xu Zhongchi,Yang Wenli,Bao Tong,Xu Fengsheng,Zhou Wenqi,Zhang Long,Jia Qi,Wang Xiaolong,Chen Jiandong,Lin Xin
Radiotherapy is a standard treatment for thoracic malignancies, but it frequently leads to radiation‑induced heart disease (RIHD), a serious and dose‑limiting complication for which no targeted therapies are currently available. Total extracts from Abelmoschus manihot (L.) (TEA), known for their cardioprotective properties, are widely used in treating various ischemic heart diseases. Here, we identify ferroptosis driven by the NOX4/SLC7A11/GPX4 axis as a core mechanism of RIHD, with GPX4 serving as the non‑redundant downstream executor. TEA effectively modulates this axis; however, it lacks cardiac selectivity, which may compromise antitumor efficacy. To overcome this barrier, we developed, characterized, and evaluated a novel nanoplatform consisting of TEA‑loaded PLGA nanoparticles conjugated with a primary cardiomyocyte‑specific homing peptide (PCM), further integrated with low-intensity focused ultrasound (LIFU)‑triggered on‑demand release (TEA@PLGA‑PCM). This system achieves superior myocardial accumulation, effectively improves cardiac function, reverses pathological remodeling, and normalizes ferroptosis markers as well as NOX4/SLC7A11/GPX4 protein expression. In summary, we successfully constructed a novel nanoplatform that represents a promising strategy for integrated targeted delivery and synergistic therapy in RIHD management. Graphical
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DOI
高影响因子
BMC GASTROENTEROLOGY
·
2026
·Vol. 26
·期 1
·120
·
IF 3.2
Teng Xiao,Sheng Shanfeng,Pan Mingyuan,Li Yuyang,Li Zheng
Background Severe acute pancreatitis (SAP) is a critical gastrointestinal disorder associated with high mortality. Dysregulated ferroptosis, an iron-dependent form of cell death, is recognized as a pivotal mechanism driving SAP progression. Although Homoplantaginin (Homo) exhibits notable anti-inflammatory and antioxidant properties, its specific role in modulating ferroptosis during SAP remains unclear. Objective To investigate whether Homo alleviates SAP by inhibiting ferroptosis via the circDNMT3B/miR-20b-5p/SLC7A11 axis. Methods C57BL/6 mice ( n = 10 per group) were randomly allocated into nine groups, including normal control, SAP model, and various intervention groups involving Homo treatment, circDNMT3B knockdown, and miR-20b-5p inhibition. SAP was induced via caerulein and LPS injections. Assessments included histopathological evaluation, serum analysis (amylase, cytokines IL-1β, IL-6, IL-18), measurement of ferroptosis markers (MDA, GSH, tissue iron), Western blotting for ferroptosis-related proteins (ACSL4, COX-2, SLC7A11, GPX4), and qRT-PCR for gene expression. The targeting relationship between miR-20b-5p and SLC7A11 was validated by dual-luciferase reporter assay. Results SAP mice demonstrated severe pancreatic injury and hallmarks of ferroptosis, including elevated inflammation, iron accumulation, increased ACSL4/COX-2 expression, and upregulation of miR-20b-5p, alongside suppressed SLC7A11 and GPX4. Homo treatment significantly mitigated pancreatic damage and reversed these ferroptosis-related changes. CircDNMT3B knockdown exacerbated SAP severity and attenuated the protective effect of Homo, indicating its dependence on circDNMT3B. Furthermore, the detrimental effects of circDNMT3B knockdown were partially rescued by concurrent inhibition of miR-20b-5p, suggesting that miR-20b-5p acts downstream of circDNMT3B within the protective pathway mediated by Homo. The dual-luciferase assay confirmed miR-20b-5p directly targets SLC7A11. Conclusion Our study demonstrates that Homo protects against SAP primarily by suppressing ferroptosis. Mechanistically, Homo upregulates circDNMT3B, which sequesters miR-20b-5p, thereby relieving its repression of SLC7A11, which in turn supports the GPX4-mediated antioxidant defense. These findings elucidate a novel molecular pathway in SAP-associated ferroptosis and highlight the circDNMT3B/miR-20b-5p/SLC7A11 axis as a promising therapeutic target.
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PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
·
2026
·
IF 4.6
Qidi Zhai,Zhisheng Guo,Chenbo Ni,Qingsheng Tang,Jie Li
Low-dose BPA enhances proliferation and migration in RCC cells. • BPA shifts redox balance: higher GSH/GSSG, lower ROS, preserved mitochondrial membrane potential. • SLC7A11 is upregulated by BPA. • BPA attenuates responses to erastin, a system xc− inhibitor. Bisphenol A (BPA) is a ubiquitous endocrine-disrupting chemical, yet its influence on renal cell carcinoma (RCC) remains unclear. We examined whether low-dose BPA alters redox regulation linked to ferroptosis susceptibility in 786-O and ACHN cells. After concentration screening, 100 nM BPA was used for mechanistic experiments. BPA enhanced proliferation and migration, increased the glutathione redox ratio (GSH/GSSG), reduced reactive oxygen species (ROS) signals, and preserved mitochondrial membrane potential. Public cancer dataset analyses prioritized SLC7A11, which was upregulated by BPA at mRNA and protein levels. Under inhibition of the cystine/glutamate antiporter system xc− with erastin, BPA co-treatment partially attenuated cytotoxicity and functional suppression. BPA increased NF-κB p65 phosphorylation, and pyrrolidine dithiocarbamate reduced p-p65 and SLC7A11 expression. These findings suggest that environmentally relevant BPA exposure may promote stress-tolerant phenotypes in RCC cells via an NF-κB–SLC7A11–associated antioxidant response.
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高影响因子
TISSUE & CELL
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2025
·
IF 2.5
Jie Liu,Yuan-Yuan Xu,Tian-Ye Gao
Background Diabetic kidney disease (DKD) is a severe microvascular complication, and ferroptosis is a major contributor to its pathogenesis. This study investigated the protective effects of Qingyu formula (QYF), a traditional Chinese medicine prescription, against ferroptosis in high glucose-induced renal injury. Methods In vitro, human renal tubular cells (human kidney 2 [HK-2]) under high glucose conditions were treated with QYF. In vivo, the induced diabetic mice received QYF interventions. Biochemical and molecular assays assessed cell viability, oxidative stress, ferroptosis markers (Fe²⁺, glutathione [GSH], malondialdehyde) and nuclear factor erythroid 2-related factor 2/solute carrier family 7 member 11/glutathione peroxidase 4 (Nrf2/SLC7A11/GPX4) pathway activity. Results Qingyu formula enhanced cell viability and reduced reactive oxygen species in high glucose-treated HK-2 cells. It mitigated ferroptosis by decreasing Fe²⁺ accumulation and increasing GSH levels both in vivo and in vitro. Mechanistically, QYF upregulated GPX4, Nrf2 and SLC7A11. In diabetic mice, it improved metabolic parameters and reduced proteinuria in a dose-dependent manner, with high doses showing efficacy similar to that of clinically used irbesartan. Conclusions Qingyu formula protects against high glucose-induced renal injury by suppressing ferroptosis via the activation of the Nrf2/SLC7A11/GPX4 pathway. These findings support QYF as a promising candidate for targeting ferroptosis in DKD. Future studies should identify its active constituents and evaluate its efficacy in clinical trials.
研究领域:
药理学
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肾脏病学
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分子生物学
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中医中药
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细胞生物学
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DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2026
·
IF 6.5
Huimin Qiu,Xinqi Tan,Quan Sheng,Na Yang,Chunming Jiang,Lulu Wang
Metabolic dysfunction-associated steatohepatitis (MASH) frequently induces renal injury, forming a “liver-kidney axis” vicious cycle. Current therapies primarily target hepatic lesions, failing to interrupt the cross-organ injury cascade, creating an urgent need for novel strategies. To explore dapagliflozin’s therapeutic efficacy and core mechanism in MASH and associated renal injury, we utilized in vitro models (free fatty acid [FFA]-induced HepG2 hepatocyte MASH model, HK2 renal tubular epithelial cell injury model, Transwell co-culture system) and an in vivo MASH mouse model induced by a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD). Results showed dapagliflozin dose-dependently improved dysregulated lipid metabolism, suppressed inflammation, and alleviated fibrosis in vitro and in mouse liver/kidney tissues, while upregulating SIRT1/PPARα and downregulating SREBP-1c to restore lipid homeostasis. Molecularly, dapagliflozin specifically bound to ferroptosis key regulator solute carrier family 7 member 11 (SLC7A11), upregulated its abnormally reduced expression, and inhibited PI3K/AKT pathway hyperactivation—an effect mediated via a “liver-kidney axis” paracrine mechanism with β-hydroxybutyrate (β-HB) as the key mediator. Additionally, SLC7A11 knockdown in cells conversely confirmed that the lipid-lowering effect of dapagliflozin is mediated by SLC7A11.Collectively, dapagliflozin forms hydrogen bonds with SLC7A11, modulates the SIRT1/PPARα/SREBP-1c axis, and inhibits PI3K/AKT, thereby exerting therapeutic effects on MASH and associated renal injury.
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PubMed
高影响因子
ORAL DISEASES
·
2024
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IF 2.9
Huiwen Chen,Yining Zhou,Yingli Liu,Wei Zhou,Lina Xu,Dihua Shang,Jing Ni,Zhongchen Song
Objectives The purpose of this study was to determine whether indoxyl sulfate (IS) is involved in alveolar bone deterioration and to elucidate the mechanism underlying alveolar bone loss in chronic kidney disease (CKD) patients. Materials and Methods Mice were divided into the control group, CP group (ligature-induced periodontitis), CKD group (5/6 nephrectomy), and CKD + CP group. The concentration of IS in the gingival crevicular fluid (GCF) was determined by HPLC. The bone microarchitecture was evaluated by micro-CT. MC3T3-E1 cells were stimulated with IS, and changes in mitochondrial morphology and ferroptosis-related factors were detected. RT-PCR, western blotting, alkaline phosphatase activity assays, and alizarin red S staining were utilized to assess how IS affects osteogenic differentiation. Results Compared with that in the other groups, alveolar bone destruction in the CKD + CP group was more severe. IS accumulated in the GCF of mice with CKD. IS activated the aryl hydrocarbon receptor (AhR) in vitro, inhibited MC3T3-E1 cell osteogenic differentiation, caused changes in mitochondrial morphology, and activated the SLC7A11/GPX4 signaling pathway. An AhR inhibitor attenuated the aforementioned changes induced by IS. Conclusions IS activated the AhR/SLC7A11/GPX4 signaling pathway, inhibited osteogenesis in MC3T3-E1 cells, and participated in alveolar bone resorption in CKD model mice through ferroptosis.
研究领域:
牙科学
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肾病学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
FITOTERAPIA
·
2023
·
IF 3.4
Nan Zhang,Junwei Zhang,Weiqi Cui,Deqiao Wu,Jingxian Zhang,Bo Wei,Lingbo Qu,Xia Xu
Artemisia argyi H.Lév. & Vaniot, a traditional Chinese medicine with a history spanning over two millennia, has been extensively used in folk medicine to treat dysmenorrhea, uterine bleeding and inflammation. Recent studies have demonstrated that the essential oil extracted from Artemisia argyi H.Lév. & Vaniot, known as AAEO, exhibits significant anti-tumor properties against liver and lung cancers. There is a scarcity of research on the potential impact of AAEO on pancreatic cancer (PC) cells. In this study, UPLC-MS/MS-based metabolomics method was established to evaluate the effect of AAEO on the proliferation of PC cells. The differential compounds included 5-oxoproline, glutamate, γ-glutamylcysteine, glutathione, arachidonic acid, adrenal acid and linoleic acid were detected by metabolomics, enriching in the γ-glutamyl cycle and polyunsaturated fatty acid metabolism, which were closely related to ferroptosis. Meanwhile, AAEO dramatically increased the levels of intracellular iron ion via up-regulation of TFR1, augmented reactive oxygen species and malondialdehyde in a dose-dependent manner by down-regulation of γ-glutamyl cycle through decreasing expressions of SLC7A11. Additionally, β-caryophyllene oxide, one of the main components of AAEO, could covalently bind to Cys in SW1990 cells to form a conjugate Cpo-Cys, resulting in the inhibition of glutathione synthesis. Importantly, the ferroptosis inhibitor deferoxamine significantly blocked the inhibitory effect of AAEO on SW1990 cells. Meanwhile, β-caryophyllene oxide, dihydro-β-ionone and α-bisabolol had strong binding force with GPX4, SLC7A11 and TFR1, respectively. These findings showed that AAEO induced ferroptosis via regulation of γ-glutamyl cycle by SLC7A11 and iron disorders by TFR1. Our study discovered AAEO as a potential therapeutic approach to induce ferroptosis to prevent or treat PC.
研究领域:
肿瘤学
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药理学
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代谢组学
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中医药
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产品关联
DOI
PubMed
高影响因子
Redox Biology
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2025
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IF 11.9
Lu Li,Yu Cao,Xiangsheng Zhang,Jiayi Guo,Ziqiang Lin,Pengyu Zhou,Chuyin Chen,Jiahao Chen,Yike Liu,Danzhi Luo,Jiurong Chen,Yingdong Deng,Peng Sun,Zhiwen Zeng,Jun Zhou
Spinal cord injury (SCI) induced neuropathic pain (NP) remains a major clinical challenge due to persistent neuroinflammation and oxidative stress. We developed an injectable methacrylated and thiolated gelatin hydrogel loaded with quercetin (MSQ) to synergistically scavenge reactive oxygen species (ROS) and inhibit microglial ferroptosis for NP alleviation and neural repair. The MSQ hydrogel exhibited rapid photocrosslinking, sustained quercetin release, and robust ROS scavenging via thiol groups and quercetin, maintaining intracellular redox homeostasis. MSQ attenuated LPS-induced ferroptosis in BV2 microglia by upregulating Nrf2 expression, promoting its nuclear translocation, and activating the Slc7a11/Gpx4 pathway, thereby reducing lipid peroxidation and inflammatory cytokine release. Network pharmacology and molecular dynamics simulations confirmed quercetin's high-affinity binding to Nrf2. In a murine SCI model, MSQ implantation significantly reduced lesion area, suppressed microglial ferroptosis, and decreased pro-inflammatory mediators (TNFα, IL-1β, IL-6), while enhancing neuronal survival (Nissl/NeuN + cells) and axonal regeneration (MAP2/5-HT + expression). Motor functional recovery assays revealed improved BMS scores, gait regularity, and mechanical/thermal pain thresholds in MSQ-treated mice. This study highlights MSQ hydrogel as a multifunctional therapeutic platform that targets ROS homeostasis and microglial ferroptosis via the Nrf2/Slc7a11/Gpx4 axis, offering a promising strategy for post-SCI NP management and neural regeneration.
研究领域:
生物材料
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神经科学
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药理学
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再生医学
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生物化学
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炎症研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2023
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IF 10.8
Chuang Yang,Zheng Chen,Min Wei,Shen Hu,Mengyuan Cai,Nan Wang,Yunan Guan,Fangyuan Li,Qiang Ding,Daishun Ling
Ferroptosis has recently become an attractive strategy to combat the chemoresistance of cancer cells, but the intracellular ferroptosis defense system greatly challenges the efficient ferroptosis induction. Herein, we report a ferrous metal-organic framework-based nanoagent (FMN) that inhibits the intracellular upstream glutathione synthesis and induces self-amplified ferroptosis of cancer cells, for reversing chemoresistance and boosting chemotherapy. The FMN is loaded with SLC7A11 siRNA (siSLC7A11) and chemotherapeutic doxorubicin (DOX), which shows enhanced tumor cell uptake and retention, thus ensuring the effective DOX delivery and tumor intracellular iron accumulation. Importantly, the FMN simultaneously catalyzes the iron-dependent Fenton reaction and triggers the siSLC7A11-mediated suppression of upstream glutathione synthesis for intracellularly self-amplified ferroptosis, which further inhibits P-glycoprotein activity for DOX retention, and regulates the expression of Bcl-2/Bax to reverse the apoptotic resistance state of tumor cells. The FMN-mediated ferroptosis is also demonstrated in ex vivo patient-derived tumor fragment platform. Consequently, FMN successfully reverses cancer chemoresistance and achieves a highly efficient in vivo therapeutic efficacy in MCF7/ADR tumor-bearing mice. Our study provides a self-amplified ferroptosis strategy via inhibiting intracellular upstream glutathione synthesis, which is effective to reverse cancer chemoresistance.
研究领域:
肿瘤学
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纳米技术
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药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2023
·
IF 7.5
Yijing Yang,Ying Wang,Ying Deng,Jing Lu,Li Xiao,Jie Li,Yasha Zhou,Fujiao Nie,Xiangdong Chen,Jun Peng,Hanyu Tan,Yuhui Qin,Qinghua Peng
Aim of the study To assess the impact of Fructus Lycii and Salvia miltiorrhiza Bunge extract (FSE) on retinitis pigmentosa (RP) and to explore the mechanisms by which FSE can prevent oxidative stress-induced photoreceptor ferroptosis in RP. Methods Hydrogen peroxide(H 2 O 2 ) was used to induce oxidative stress in 661 W cells, which were then examined using flow cytometry and enzyme linked immunosorbent assay (ELISA). Changes in mitochondria were observed by using an electron microscope to characterize the ferroptosis of the cells. The protective effect of FSE on the retina function and structure of rd10 mice was evaluated using histopathological examination, fundus photographs, and electroretinography (ERG). Protein expression levels of Tumor Protein p53 (P53), Solute Carrier Family 7 Member 11 (SLC7A11), Glutathione peroxidase 4 (GPX4), Arachidonate-12-Lipoxygenase (ALOX12), and Dipeptidyl peptidase 4 (DPP4) were evaluated by Western blot assays in Vivo and in Vitro. Results H 2 O 2 -induced 661 W cells increased oxidative stress products and P53 and ALOX12, decreasing the expression of SLC7A11, GPX4, and DPP4. GPX4 activator does not reduce reactive oxygen species (ROS) generation and has little effect on ferroptosis. Fer-1 and FSE attenuate ROS generation and inhibit ferroptosis of photoreceptors in RP via inhibited P53 expression and increased SLC7A11 and GPX4 expression. Conclusion FSE may be available in clinical therapeutics to alleviating RP and the mechanism by which inhibits ferroptosis of photoreceptors following oxidative stress via the P53/ SLC7A11 pathway.
研究领域:
眼科学
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药理学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Biomaterials Research
·
2023
·Vol. 27
·期 1
·1-17
·
IF 11.3
Xiao Youmei,Xu Zhanxue,Cheng Yuan,Huang Rufan,Xie Yuan,Tsai Hsiang-i,Zha Hualian,Xi Lifang,Wang Kai,Cheng Xiaoli,Gao Yanfeng,Zhang Changhua,Cheng Fang,Chen Hongbo
Background Ferroptosis, iron-dependent cell death, is an established mechanism for cancer suppression, particularly in hepatocellular carcinoma (HCC). Sorafenib (SOR), a frontline drug for the treatment of HCC, induces ferroptosis by inhibiting the Solute Carrier family 7 member 11 (SLC7A11), with inadequate ferroptosis notably contributing to SOR resistance in tumor cells. Methods To further verify the biological targets associated with ferroptosis in HCC, an analysis of the Cancer Genome Atlas (TCGA) database was performed to find a significant co-upregulation of SLC7A11 and transferrin receptor (TFRC), Herein, cell membrane-derived transferrin nanovesicles (TF NVs) coupled with Fe 3+ and encapsulated SOR (SOR@TF-Fe 3+ NVs) were established to synergistically promote ferroptosis, which promoted the iron transport metabolism by TFRC/TF-Fe 3+ and enhanced SOR efficacy by inhibiting the SLC7A11. Results In vivo and in vitro experiments revealed that SOR@TF-Fe 3+ NVs predominantly accumulate in the liver, and specifically targeted HCC cells overexpressing TFRC. Various tests demonstrated SOR@TF-Fe 3+ NVs accelerated Fe 3+ absorption and transformation in HCC cells. Importantly, SOR@TF-Fe 3+ NVs were more effective in promoting the accumulation of lipid peroxides (LPO), inhibiting tumor proliferation, and prolonging survival rates in HCC mouse model than SOR and TF- Fe 3+ NVs alone. Conclusions The present work provides a promising therapeutic strategy for the targeted treatment of HCC. Graphical abstract
研究领域:
肿瘤学
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药理学
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纳米技术
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分子生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）