Tagitinin C induces ferroptosis through PERK-Nrf2-HO-1 signaling pathway in colorectal cancer cells

International Journal of Biological Sciences, Journal Year: 2021, Volume and Issue: 17(11), P. 2703 - 2717

Published: Jan. 1, 2021

Rationale: Colorectal cancer (CRC) is a common malignant tumor of the digestive system. However, efficacy surgery and chemotherapy limited. Ferroptosis an iron- reactive oxygen species (ROS)-dependent form regulated cell death (RCD) plays vital role in suppression. inducing agents have been studied extensively as novel promising way to fight against therapy resistant cancers. The aim this study investigate mechanism action tagitinin C (TC), natural product, ferroptosis inducer Methods: response CRC cells was assessed by viability assay, clonogenic transwell migration cycle assay apoptosis assay. Molecular approaches including Western blot, RNA sequencing, quantitative real-time PCR immunofluorescence were employed well. Results: Tagitinin C, sesquiterpene lactone isolated from Tithonia diversifolia, inhibits growth colorectal HCT116 cells, induced oxidative cellular microenvironment resulting cells. C-induced accompanied with attenuation glutathione (GSH) levels increased lipid peroxidation. Mechanistically, endoplasmic reticulum (ER) stress stress, thus activating nuclear translocation factor erythroid 2-related 2 (Nrf2). As downstream gene (effector) Nrf2, heme oxygenase-1 (HO-1) expression significantly treatment C. Upregulated HO-1 led increase labile iron pool, which promoted peroxidation, meanwhile showed synergistic anti-tumor effect together erastin. Conclusion: In summary, we provided evidence that induces has through ER stress-mediated activation PERK-Nrf2-HO-1 signaling pathway. identified inducer, may be effective chemosensitizer can expand range chemotherapeutic agents.

Language: Английский

---

Bavachin Induces Ferroptosis through the STAT3/P53/SLC7A11 Axis in Osteosarcoma Cells

Oxidative Medicine and Cellular Longevity, Journal Year: 2021, Volume and Issue: 2021(1)

Published: Jan. 1, 2021

Ferroptosis is a new form of regulated cell death, which mediated by intracellular iron. Although it reported that bavachin has antitumour effects on several tumour cells and prompts the reactive oxygen species (ROS) generation, unclear whether ferroptosis can be induced in osteosarcoma (OS) cells. In this study, we found inhibits viability MG63 HOS OS lines along with an increase ferrous iron level, ROS accumulation, malondialdehyde overexpression, glutathione depletion. Moreover, chelators (deferoxamine), antioxidants (Vit E), inhibitors (ferrostatin-1 liproxstatin-1) reverse bavachin-induced death. Bavachin also altered mitochondrial morphology cells, leading to smaller mitochondria, higher density membrane, reduced cristae. Further investigation showed upregulated expression transferrin receptor, divalent metal transporter-1, P53, downregulating ferritin light chain, heavy p-STAT3 (705), SLC7A11, peroxidase-4 More importantly, STAT3 SLC7A11 pretreatment pifithrin-α (P53 inhibitor) rescued bavachin. The results show induces via STAT3/P53/SLC7A11 axis

Language: Английский

---

Ferroptosis and ferritinophagy in diabetes complications

Molecular Metabolism, Journal Year: 2022, Volume and Issue: 60, P. 101470 - 101470

Published: March 15, 2022

With long-term metabolic malfunction, diabetes can cause serious damage to whole-body tissue and organs, resulting in a variety of complications. Therefore, it is particularly important further explore the pathogenesis complications develop drugs for prevention treatment. In recent years, different from apoptosis necrosis, ferroptosis has been recognized as new regulatory mode cell death involves regulation nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy. Evidence shows that ferritinophagy play significant role occurrence development

Language: Английский

---

Role and mechanism of ferroptosis in neurological diseases

Molecular Metabolism, Journal Year: 2022, Volume and Issue: 61, P. 101502 - 101502

Published: April 19, 2022

Ferroptosis, as a new form of cell death, is different from other deaths such autophagy or senescence. Ferroptosis involves in the pathophysiological progress several diseases, including cancers, cardiovascular nervous system and kidney damage. Since oxidative stress iron deposition are broad pathological features neurological role ferroptosis diseases has been widely explored. mainly characterized by changes homeostasis, iron-dependent lipid peroxidation, glutamate toxicity accumulation, which can be specifically reversed inducers inhibitors. The regulated metabolism iron, lipids amino acids through System Xc−, voltage-dependent anion channels, p53, p62-Keap1-Nrf2, mevalonate pathways. This review also focus on regulatory pathways its research diseases. current researches mostly key ferroptosis. At same time, was found playing bidirectional regulation Therefore, specific mechanisms still need to further explored provide perspectives for application treatment

Language: Английский

---

International consensus guidelines for the definition, detection, and interpretation of autophagy-dependent ferroptosis

Autophagy, Journal Year: 2024, Volume and Issue: 20(6), P. 1213 - 1246

Published: March 6, 2024

Macroautophagy/autophagy is a complex degradation process with dual role in cell death that influenced by the types are involved and stressors they exposed to. Ferroptosis an iron-dependent oxidative form of characterized unrestricted lipid peroxidation context heterogeneous plastic mechanisms. Recent studies have shed light on involvement specific autophagy (e.g. ferritinophagy, lipophagy, clockophagy) initiating or executing ferroptotic through selective anti-injury proteins organelles. Conversely, other forms reticulophagy lysophagy) enhance cellular defense against damage. Dysregulated autophagy-dependent ferroptosis has implications for diverse range pathological conditions. This review aims to present updated definition ferroptosis, discuss influential substrates receptors, outline experimental methods, propose guidelines interpreting results.

Language: Английский

---

Ferroptosis‐modulating small molecules for targeting drug‐resistant cancer: Challenges and opportunities in manipulating redox signaling

Medicinal Research Reviews, Journal Year: 2023, Volume and Issue: 43(3), P. 614 - 682

Published: Jan. 19, 2023

Abstract Ferroptosis is an iron‐dependent cell death program that characterized by excessive lipid peroxidation. Triggering ferroptosis has been proposed as a promising strategy to fight cancer and overcome drug resistance in antitumor therapy. Understanding the molecular interactions structural features of ferroptosis‐inducing compounds might therefore open door efficient pharmacological strategies against aggressive, metastatic, therapy‐resistant cancer. We here summarize mechanisms requirements small molecules target central players ferroptosis. Focus placed on (i) glutathione peroxidase (GPX) 4, only GPX isoenzyme detoxifies complex membrane‐bound hydroperoxides, (ii) cystine/glutamate antiporter system X c − for regeneration, (iii) redox‐protective transcription factor nuclear erythroid 2‐related (NRF2), (iv) GPX4 repression combination with induced heme degradation via oxygenase‐1. deduce common ferroptotic activity highlight challenges development. Moreover, we critically discuss potential natural products lead structures provide comprehensive overview structurally diverse biogenic bioinspired trigger iron oxidation, inhibition thioredoxin/thioredoxin reductase or less defined modes action.

Language: Английский

---

Ferroptosis: a novel regulated cell death participating in cellular stress response, radiotherapy, and immunotherapy

Experimental Hematology and Oncology, Journal Year: 2023, Volume and Issue: 12(1)

Published: July 27, 2023

Abstract Background Ferroptosis is a regulated cell death mode triggered by iron-dependent toxic membrane lipid peroxidation. As novel modality that morphologically and mechanistically different from other forms of death, such as apoptosis necrosis, ferroptosis has attracted extensive attention due to its association with various diseases. Evidence on potential therapeutic strategy accumulated the rapid growth research targeting for tumor suppression in recent years. Methods We summarize currently known characteristics major regulatory mechanisms present role cellular stress responses, including ER autophagy. Furthermore, we elucidate applications radiotherapy immunotherapy, which will be beneficial exploring new strategies clinical treatment. Result conclusion Based specific biomarkers precise patient-specific assessment, great translated into practical approaches cancer therapy, significantly contributing prevention, diagnosis, prognosis, treatment cancer.

Language: Английский

---

Natural Flavonoid Apigenin, an Effective Agent Against Nervous System Cancers

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 61(8), P. 5572 - 5583

Published: Jan. 11, 2024

Language: Английский

---

Curcumin Induces Autophagy-mediated Ferroptosis by Targeting the PI3K/AKT/mTOR Signaling Pathway in Gastric Cancer

The Turkish Journal of Gastroenterology, Journal Year: 2025, Volume and Issue: 35(8), P. 625 - 633

Published: April 8, 2025

As a very common malignancy of the digestive system, incidence and mortality rates gastric cancer (GC) are increasing year by year. The critical role ferroptosis in development has been well-documented. polyphenol compound curcumin shows prominent anti-tumor effects multiple types, including GC. However, whether participates GC tumorigenesis regulating remains unknown. Gastric cells AGS HGC-27 were treated with (0, 10, 20 μM). Cell viability death evaluated through CCK-8 LDH release assays. LC3B expression was estimated immunofluorescence staining. Intracellular ferrous iron (Fe2+), GSH, MDA, lipid ROS levels assessed corresponding assay kits. cellular autophagy markers (ATG5, ATG7, Beclin 1, LC3B), (ACSL4, SLC7A11, GPX4), phosphorylated (p)-PI3K, p-AKT, p-mTOR determined western blotting. Curcumin attenuated cell but stimulated cells. enhanced cells, as demonstrated increased ATG5, LC3B. Besides, upregulated iron, ACSL4 while downregulated ROS, GPX4 levels, suggesting its stimulation on decreased p-PI3K, Importantly, inhibitor ferrostatin-1 overturned impacts viability, death, ferroptosis. suppresses inducing autophagy-mediated inactivating PI3K/AKT/mTOR signaling.

Language: Английский

---

Immunogenic ferroptosis and where to find it?

Journal for ImmunoTherapy of Cancer, Journal Year: 2021, Volume and Issue: 9(12), P. e003430 - e003430

Published: Dec. 1, 2021

Ferroptosis is a recently discovered form of regulated cell death that morphologically, genetically, and biochemically distinct from apoptosis necroptosis, its potential use in anticancer therapy emerging. The strong immunogenicity (early) ferroptotic cancer cells broadens the current concept immunogenic opens up new possibilities for treatment. In particular, induction ferroptosis could be beneficial patients with cancers resistant to necroptosis. However, may rich source oxidized lipids, which contribute decreased phagocytosis antigen cross-presentation by dendritic thus favor tumor evasion. This explain non-immunogenicity late cells. Besides presence lactate microenvironment, acidification hypoxia are essential factors promoting resistance affecting immunogenicity. Here, we critically discuss crucial mediators controlling modulate antitumor immunity. We emphasize it will necessary also identify tolerogenic (ie, immunosuppressive) nature ferroptosis, can lead

Language: Английский

---