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

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Ferroptosis as a potential target for cancer therapy

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(7)

Published: July 24, 2023

Abstract Ferroptosis is a recently discovered essential type of cell death that mainly characterized by iron overload and lipid peroxidation. Emerging evidence suggests ferroptosis double-edged sword in human cancer. However, the precise underlying molecular mechanisms their differential roles tumorigenesis are unclear. Therefore, this review, we summarize briefly present key pathways ferroptosis, paying special attention to regulation as well its dual role an oncogenic tumor suppressor event various cancers. Moreover, multiple pharmacological activators summarized, prospect targeting cancer therapy further elucidated.

Language: Английский

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N‐acetyltransferase 10 promotes colon cancer progression by inhibiting ferroptosis through N4‐acetylation and stabilization of ferroptosis suppressor protein 1 (FSP1) mRNA

Cancer Communications, Journal Year: 2022, Volume and Issue: 42(12), P. 1347 - 1366

Published: Oct. 8, 2022

Abstract Background N‐acetyltransferase 10 ( NAT10 ) is the only enzyme known to mediate N4‐acetylcytidine (ac4C) modification of mRNA and crucial for stability translation efficiency. However, its role in cancer development prognosis has not yet been explored. This study aimed examine possible colon cancer. Methods The expression levels were evaluated by immunohistochemical analyses with a tissue microarray, prognostic value patients was further analyzed. Quantitative real‐time polymerase chain reaction (qRT‐PCR) Western blotting performed analyze harvested tissues cell lines. Stable ‐knockdown ‐overexpressing lines constructed using lentivirus. biological functions analyzed vitro Cell Counting Kit‐8 (CCK‐8), wound healing, Transwell, cycle, ferroptosis assays. Xenograft models used effect on tumorigenesis metastasis cells vivo. Dot blotting, acetylated RNA immunoprecipitation‐qPCR, explore mechanism which progression. Results upregulated various increased associated shorter patient survival. Knockdown two (HT‐29 LoVo) impaired proliferation, migration, invasion, tumor formation these cells, whereas overexpression promoted abilities. Further analysis revealed that exerted strong suppressor protein 1 FSP1 HT‐29 LoVo cells. In found be modified ac4C acetylation, this epigenetic inhibition ferroptosis. Conclusions Our plays critical affecting ferroptosis, suggesting could novel therapeutic target

Language: Английский

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Evidence of pyroptosis and ferroptosis extensively involved in autoimmune diseases at the single-cell transcriptome level

Journal of Translational Medicine, Journal Year: 2022, Volume and Issue: 20(1)

Published: Aug. 12, 2022

Approximately 8-9% of the world's population is affected by autoimmune diseases, and yet mechanism autoimmunity trigger largely understudied. Two unique cell death modalities, ferroptosis pyroptosis, provide a new perspective on mechanisms leading to development treatment strategies.Using scRNA-seq datasets, aberrant trend pyroptosis-related genes were analyzed in several representative diseases (psoriasis, atopic dermatitis, vitiligo, multiple sclerosis, systemic sclerosis-associated interstitial lung disease, Crohn's experimental orchitis). Cell line models also assessed using bulk RNA-seq qPCR.A substantial difference was observed between normal disease samples involving pyroptosis. In present study, pyroptosis showed an imbalance different keratinocyte lineages psoriatic skinin addition pyroptosis-sensitive subset dermatitis (AD) skin. The results revealed that are involved epidermal melanocyte destruction vitiligo. Aberrant has been detected orchitis. adopted study identified pro-inflammatory factors can drive changes pyroptosis.These involvement pathological process at level. IFN-γ critical inducer sensitivity, two models.

Language: Английский

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Breast Cancer Stem-Like Cells in Drug Resistance: A Review of Mechanisms and Novel Therapeutic Strategies to Overcome Drug Resistance

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: March 21, 2022

Breast cancer is the most frequent type of malignancy in women worldwide, and drug resistance to available systemic therapies remains a major challenge. At molecular level, breast heterogeneous, where cancer-initiating stem-like cells (bCSCs) comprise small yet distinct population within tumor microenvironment (TME) that can differentiate into multiple lineages, displaying varying degrees cellular differentiation, enhanced metastatic potential, invasiveness, radio- chemotherapy. Based on expression estrogen progesterone hormone receptors, human epidermal growth factor receptor 2 (HER2), and/or BRCA mutations, subtypes are identified as TNBC, HER2 enriched, luminal A, B. Management primarily involves resection tumor, followed by radiotherapy, including endocrine for hormone-responsive cancers; HER2-targeted therapy HER2-enriched chemotherapy poly (ADP-ribose) polymerase inhibitors recent development immunotherapy. However, complex crosstalk between malignant stromal TME, rewiring many different signaling networks, bCSC-mediated processes, all contribute overall cancer. strategically targeting bCSCs reverse chemoresistance increase sensitivity an underexplored stream research. The identification dysregulated miRNAs/ncRNAs/mRNAs signatures their with pathways has uncovered promising leads be used potential therapeutic targets drug-resistant situations. Moreover, induce alternate forms regulated cell death ferroptosis, pyroptosis, immunotherapy; drugs bCSC metabolism; nanoparticle upcoming approaches target overcome resistance. Thus, individualizing treatment strategies will eliminate minimal residual disease, resulting better pathological complete response scenarios. This review summarizes basic understanding subtypes, concept bCSCs, basis resistance, miRNAs/ncRNAs patterns future perspective developing anticancer therapeutics address

Language: Английский

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Ferroptosis as a Novel Therapeutic Target for Diabetes and Its Complications

Frontiers in Endocrinology, Journal Year: 2022, Volume and Issue: 13

Published: March 29, 2022

The global diabetes epidemic and its complications are increasing, thereby posing a major threat to public health. A comprehensive understanding of mellitus (DM) is necessary for the development effective treatments. Ferroptosis newly identified form programmed cell death caused by production reactive oxygen species an imbalance in iron homeostasis. Increasing evidence suggests that ferroptosis plays pivotal role pathogenesis diabetes-related complications. In this review, we summarize potential impact regulatory mechanisms on complications, as well inhibitors diabetic Therefore, developing drugs or agents target may provide new treatment strategies patients with diabetes.

Language: Английский

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Ferroptosis in life: To be or not to be

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 159, P. 114241 - 114241

Published: Jan. 10, 2023

Ferroptosis is a novel type of programmed cell death, characterized by dysregulated iron metabolism and accumulation lipid peroxides. It features the alteration mitochondria aberrant excessive as well loss cysteine-glutathione-GPX4 axis. Eventually, accumulated peroxides result in lethal damage to cells. induced overloading ROS can be inhibited activation GPX4 pathway, FS1-CoQ10 GCH1-BH4 DHODH it also regulated oncogenes tumor suppressors. involves various physiological pathological processes, increasing evidence indicates that ferroptosis play critical role cancers other diseases. inhibits proliferation malignant cells types inducing may become new method cancer treatment. Many inhibitors targeting key factors such SLC7A11, GPX4, overload have been developed. The application mainly divided into two directions, i.e. avoid healthy selectively induce cancers. In this review, we provide analysis concept, regulation pathways explored its roles diseases, summarized compounds ferroptosis, aiming promote speed clinical use induction

Language: Английский

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Acidosis activates breast cancer ferroptosis through ZFAND5/SLC3A2 signaling axis and elicits M1 macrophage polarization

Cancer Letters, Journal Year: 2024, Volume and Issue: 587, P. 216732 - 216732

Published: Feb. 14, 2024

Language: Английский

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Identification of the prognostic value of ferroptosis-related gene signature in breast cancer patients

BMC Cancer, Journal Year: 2021, Volume and Issue: 21(1)

Published: May 31, 2021

Abstract Background Breast cancer (BRCA) is a malignant tumor with high morbidity and mortality, which threat to women’s health worldwide. Ferroptosis closely related the occurrence development of breast cancer. Here, we aimed establish ferroptosis-related prognostic gene signature for predicting patients’ survival. Methods Gene expression profile corresponding clinical information patients from The Cancer Genome Atlas (TCGA) database Expression Omnibus (GEO) database. Least absolute shrinkage selection operator (LASSO)-penalized Cox regression analysis model was utilized construct multigene signature. Kaplan-Meier (K-M) Receiver Operating Characteristic (ROC) curves were plotted validate predictive effect Ontology (GO) Kyoto Encyclopedia Genes, Genomes (KEGG) pathway single-sample set enrichment (ssGSEA) performed between high-risk low-risk groups divided by median value risk score. Results We constructed consisted nine genes (ALOX15, CISD1, CS, GCLC, GPX4, SLC7A11, EMC2, G6PD ACSF2). validated fine accuracy ( p < 0.001). area under curve (AUC) ROC manifested that had moderate power. GO KEGG functional revealed immune-related responses largely enriched, immune cells, including activated dendritic cells (aDCs), (DCs), T-helper 1 (Th1), higher in Oppositely, type I IFN response II lower Conclusion Our study indicated could serve as novel biomarker prognosis. Furthermore, found immunotherapy might play vital role therapeutic schedule based on level difference pathways different patients.

Language: Английский

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xCT-Driven Expression of GPX4 Determines Sensitivity of Breast Cancer Cells to Ferroptosis Inducers

Antioxidants, Journal Year: 2021, Volume and Issue: 10(2), P. 317 - 317

Published: Feb. 20, 2021

Inducers of ferroptosis such as the glutathione depleting agent Erastin and GPX4 inhibitor Rsl-3 are being actively explored potential therapeutics in various cancers, but factors that determine their sensitivity poorly understood. Here, we show expression levels both subunits cystine/glutamate antiporter xCT breast cancer, upregulation xCT/selenocysteine biosynthesis/GPX4 production axis paradoxically renders cancer cells more sensitive to certain types ferroptotic stimuli. We find is strongly upregulated a subset tissues compared matched normal samples, this tightly correlated with increased SLC7A11 SLC3A2. depletes antioxidant selenoproteins GPX1 by inhibiting xCT-dependent extracellular reduction which required for selenium uptake selenocysteine biosynthesis. Unexpectedly, while resistant nontransformed against oxidative stress inducing drugs, at same time they hypersensitive lipid peroxidation induced or Rsl-3, indicating ‘addicted’ xCT/GPX4 axis. Our findings provide strategic basis targeting anti-ferroptotic machinery depending on status, can be further explored.

Language: Английский

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