Melatonin ameliorates oxidative stress-mediated injuries through induction of HO-1 and restores autophagic flux in dry eye DOI Creative Commons
Bowen Wang,

Xin Zuo,

Lulu Peng

et al.

Experimental Eye Research, Journal Year: 2021, Volume and Issue: 205, P. 108491 - 108491

Published: Feb. 15, 2021

This study aimed to investigate the protective effect of melatonin on corneal epithelium in dry eye disease(DED) and explore its underlying mechanism. Human epithelial(HCE) cells was exposure t-butylhydroperoxide(tBH), C57BL/6 mice were injected subcutaneous scopolamine imitate DED. Melatonin used both vivo vitro. Cell viability detected by Counting Kit-8 assay Lactate Dehydrogenase Leakage. The change cellular reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP), apoptosis analyzed flow cytometry. Western blot assays immunofluorescence carried out measure protein changes. mRNA expression investigated RNA sequencing (RNA-Seq) quantitative real-time PCR. autophagic flux observed through mCherry-GFP-LC3 transfection electron microscopy(TEM). Clinical parameters defects, conjunctival goblet cells, tear volume, level ocular surface inflammation recorded. able reduce excessive ROS production maintain function. TEM found rescued impaired under tBH. Moreover, significantly preserved cell viability, abolished LDH release, decreased apoptosis. RNA-Seq indicated that greatly activating hemeoxygenase-1 (HO-1) expression. Interestingly, HO-1 ablation largely attenuated effects. Besides, mouse model, intraperitoneal injection showed improved clinical parameters, inhibited activated NLRP3 cascade, increased density volume. Thus, protects epithelial from oxidative damage, normal autophagy, via trigging

Language: Английский

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

Ruiran Wei,

Yueqin Zhao,

Juan Wang

et al.

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

Citations

291
Long noncoding RNA LINC01606 protects colon cancer cells from ferroptotic cell death and promotes stemness by SCD1–Wnt/β‐catenin–TFE3 feedback loop signalling DOI

Yajun Luo,

Siqi Huang, Jinlai Wei

et al.

Clinical and Translational Medicine, Journal Year: 2022, Volume and Issue: 12(4)

Published: April 1, 2022

Language: Английский

Citations

74
Ferroptosis, Necroptosis, and Pyroptosis in Gastrointestinal Cancers: The Chief Culprits of Tumor Progression and Drug Resistance DOI Creative Commons
Xudong Zhu, Shenglong Li

Advanced Science, Journal Year: 2023, Volume and Issue: 10(26)

Published: July 12, 2023

In recent years, the incidence of gastrointestinal cancers is increasing, particularly in younger population. Effective treatment crucial for improving patients' survival outcomes. Programmed cell death, regulated by various genes, plays a fundamental role growth and development organisms. It also critical maintaining tissue organ homeostasis takes part multiple pathological processes. addition to apoptosis, there are other types programmed such as ferroptosis, necroptosis, pyroptosis, which can induce severe inflammatory responses. Notably, besides pyroptosis contribute occurrence cancers. This review aims provide comprehensive summary on biological roles molecular mechanisms well their regulators hope open up new paths tumor targeted therapy near future.

Language: Английский

Citations

44
Targeting SLC7A11 specifically suppresses the progression of colorectal cancer stem cells via inducing ferroptosis DOI
Xiaotian Xu, Xiyang Zhang,

Chengqiong Wei

et al.

European Journal of Pharmaceutical Sciences, Journal Year: 2020, Volume and Issue: 152, P. 105450 - 105450

Published: July 2, 2020

Language: Английский

Citations

124
Association of oral dysbiosis with oral cancer development (Review) DOI Open Access
Giusy Rita Maria La Rosa, Giuseppe Gattuso,

Eugenio Pedull�

et al.

Oncology Letters, Journal Year: 2020, Volume and Issue: unknown

Published: March 3, 2020

Oral squamous cell carcinoma (OSCC) is the leading cause of mortality for oral cancer. Numerous risk factors mainly related to unhealthy habits and responsible chronic inflammation infections have been recognized as predisposing carcinogenesis. Recently, even microbiota alterations associated with development human cancers. In particular, some specific bacterial strains strongly cancer (Capnocytophaga gingivalis, Fusobacterium spp., Streptococcus Peptostreptococcus Porphyromonas gingivalis Prevotella spp.). Several hypotheses proposed explain how could be involved in pathogenesis by paying attention inflammation, microbial synthesis cancerogenic substances, alteration epithelial barrier integrity. Based on knowledge carcinogenic effects dysbiosis, it was recently suggested that probiotics may anti-tumoral activity. Nevertheless, few data exist regard probiotic On this basis, association between dysbiosis discussed focusing potential benefits administration prevention.

Language: Английский

Citations

92
RETRACTED: Amentoflavone suppresses cell proliferation and induces cell death through triggering autophagy-dependent ferroptosis in human glioma DOI
Yan Chen, Ning Li, Haijing Wang

et al.

Life Sciences, Journal Year: 2020, Volume and Issue: 247, P. 117425 - 117425

Published: Feb. 11, 2020

Language: Английский

Citations

84
RETRACTED: Physcion 8-O-β-glucopyranoside induced ferroptosis via regulating miR-103a-3p/GLS2 axis in gastric cancer DOI
Yingjie Niu, Jinping Zhang, Yalin Tong

et al.

Life Sciences, Journal Year: 2019, Volume and Issue: 237, P. 116893 - 116893

Published: Oct. 10, 2019

Language: Английский

Citations

80
Inhibitory Effect and Mechanism of Action of Quercetin and Quercetin Diels-Alder anti-Dimer on Erastin-Induced Ferroptosis in Bone Marrow-Derived Mesenchymal Stem Cells DOI Creative Commons
Xican Li,

Jingyuan Zeng,

Yangping Liu

et al.

Antioxidants, Journal Year: 2020, Volume and Issue: 9(3), P. 205 - 205

Published: March 2, 2020

In this study, the anti-ferroptosis effects of catecholic flavonol quercetin and its metabolite Diels-Alder anti-dimer (QDAD) were studied using an erastin-treated bone marrow-derived mesenchymal stem cell (bmMSCs) model. Quercetin exhibited higher levels than QDAD, as indicated by 4,4-difluoro-5-(4-phenyl-1,3-butadienyl)-4-bora-3a,4a-diaza-s-indacene-3-undecanoic acid (C11-BODIPY), 2′,7′-dichlorodihydrofluoroscein diacetate (H2DCFDA), lactate dehydrogenase (LDH) release, counting kit-8 (CCK-8), flow cytometric assays. To understand possible pathways involved, reaction product with 1,1-diphenyl-2-picrylhydrazyl radical (DPPH●) was measured ultra-performance liquid-chromatography coupled electrospray-ionization quadrupole time-of-flight tandem mass spectrometry (UHPLC-ESI-Q-TOF-MS). found to produce same clusters molecular ion peaks fragments standard QDAD. Furthermore, antioxidant QDAD compared determining their 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide radical-scavenging, Cu2+-reducing, Fe3+-reducing, lipid peroxidation-scavenging, DPPH●-scavenging activities. consistently showed lower IC50 values These findings indicate that can protect bmMSCs from erastin-induced ferroptosis, possibly through pathway. The pathway convert into QDAD—an inferior ferroptosis-inhibitor antioxidant. weakening has highlighted a rule for predicting relative flavonols dimer metabolites.

Language: Английский

Citations

71
Ferroptosis: Cancer Stem Cells Rely on Iron until “to Die for” It DOI Creative Commons
Emma Cosialls, Rima Elhage, Leïla Dos Santos

et al.

Cells, Journal Year: 2021, Volume and Issue: 10(11), P. 2981 - 2981

Published: Nov. 2, 2021

Cancer stem cells (CSCs) are a distinct subpopulation of tumor with cell-like features. Able to initiate and sustain growth mostly resistant anti-cancer therapies, they thought responsible for recurrence metastasis. Recent accumulated evidence supports that iron metabolism the recent discovery ferroptosis constitutes promising new lead in field anti-CSC therapeutic strategies. Indeed, uptake, efflux, storage regulation pathways all over-engaged microenvironment suggesting reprogramming is crucial occurrence cell survival. In particular, studies have highlighted importance maintenance CSCs. Furthermore, high concentration found CSCs, as compared non-CSCs, underlines their addiction. line this, if an essential macronutrient nevertheless highly reactive, it represents Achilles’ heel by inducing death therefore providing opportunities target this review, we first summarize our current understanding its Then, provide overview knowledge discuss role autophagy (regulation of) ferroptotic pathways. Finally, potential strategies could be used CSCs treat cancer.

Language: Английский

Citations

65
HO-1 Contributes to Luteolin-Triggered Ferroptosis in Clear Cell Renal Cell Carcinoma via Increasing the Labile Iron Pool and Promoting Lipid Peroxidation DOI Creative Commons
Shangting Han, Fangyou Lin, Yucheng Qi

et al.

Oxidative Medicine and Cellular Longevity, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 26

Published: April 25, 2022

Ferroptosis, a novel form of regulated cell death characterized by disrupted iron metabolism and the accumulation lipid peroxides, has exhibited enormous potential in therapy cancer particularly clear renal carcinoma (ccRCC). Luteolin (Lut), natural flavonoid widely existing various fruits vegetables, been proven to exert potent anticancer activity vitro vivo. However, previous studies on mechanism Lut have shown apoptosis but not ferroptosis. In present study, we identified that substantially inhibited survival ccRCC vivo, this phenomenon was accompanied excessively increased intracellular Fe2+ abnormal depletion GSH. addition, induced imbalance mitochondrial membrane potential, classical morphological alterations ferroptosis, generation ROS, occurrence peroxidation an iron-dependent manner cells. these could be reversed some extent ion chelator deferiprone or ferroptosis inhibitor ferrostatin-1, indicating cells treated with underwent Mechanistically, molecular docking further established probably promoted heme degradation labile pool (LIP) upregulating HO-1 expression, which led Fenton reaction, GSH depletion, ccRCC, whereas blocking signaling pathway evidently rescued Lut-induced inhibiting Altogether, current study shows compound monomer exerted efficacy expression activating LIP trigger promising drug candidate for treatment.

Language: Английский

Citations

65