The Role of HO-1 and Its Crosstalk with Oxidative Stress in Cancer Cell Survival

Cells, Journal Year: 2021, Volume and Issue: 10(9), P. 2401 - 2401

Published: Sept. 13, 2021

Heme oxygenases (HOs) act on heme degradation to produce carbon monoxide (CO), free iron, ferritin, and biliverdin. Upregulation of cellular HO-1 levels is signature oxidative stress for its downstream effects particularly under pro-oxidative status. Subcellular traffics different organelles constitute a network interactions compromising variety effectors such as pro-oxidants, ROS, mitochondrial enzymes, nucleic transcription factors. Some the compartmentalized have been demonstrated functioning in progression cancer. Emerging data show multiple roles tumorigenesis from pathogenesis malignancy, metastasis, even resistance therapy. However, role has not systematically addressed. This review describes crosstalk between stress, following redox regulation tumorigenesis. HO-1-regulated signaling pathways are also summarized. aims integrate basic information current progress cancer research order enhance understandings facilitate studies.

Language: Английский

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The Diverse Roles of Heme Oxygenase-1 in Tumor Progression

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: March 31, 2021

Heme oxygenase-1 (HO-1) is an inducible intracellular enzyme that expressed in response to a variety of stimuli degrade heme, which generates the biologically active catabolites carbon monoxide (CO), biliverdin and ferrous iron (Fe 2+ ). HO-1 across range cancers has been demonstrated promote tumor progression through mechanisms. can be cells within microenvironment (TME), including both malignant as well stromal cell populations such macrophages, dendritic regulatory T-cells. Intrinsically cell, activity provides antioxidant, anti-apoptotic cytoprotective effects via its clearing toxic heme. However, heme degradation also diffuse outside extrinsically modulate wider TME, influencing cellular functionality biological processes progression, facilitating angiogenesis metastasis, promoting anti-inflammation immune suppression. Pharmacological inhibition promising therapeutic approach anti-tumor responses inhibit metastasis. these functions might context, TME type-dependent there conflicting reports for anti-tumoral processes. This review will consider our current understanding role cancer target cancer.

Language: Английский

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Control of tumor-associated macrophage responses by nutrient acquisition and metabolism

Immunity, Journal Year: 2023, Volume and Issue: 56(1), P. 14 - 31

Published: Jan. 1, 2023

Language: Английский

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An integrated single-cell reference atlas of the human endometrium

Nature Genetics, Journal Year: 2024, Volume and Issue: 56(9), P. 1925 - 1937

Published: Aug. 28, 2024

The complex and dynamic cellular composition of the human endometrium remains poorly understood. Previous endometrial single-cell atlases profiled few donors lacked consensus in defining cell types. We introduce Human Endometrial Cell Atlas (HECA), a high-resolution reference atlas (313,527 cells) combining published new transcriptomics datasets 63 women with without endometriosis. HECA assigns identifies previously unreported types, mapped situ using spatial validated independent single-nuclei dataset (312,246 nuclei, donors). In functionalis, we identify intricate stromal-epithelial coordination via transforming growth factor beta (TGFβ) signaling. basalis, define signaling between fibroblasts an epithelial population expressing progenitor markers. Integration large-scale endometriosis genome-wide association study data pinpoints decidualized stromal cells macrophages as most likely dysregulated is valuable resource for studying physiology disorders, guiding microphysiological vitro systems development.

Language: Английский

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Hematopoietic aging promotes cancer by fueling IL-1⍺–driven emergency myelopoiesis

Science, Journal Year: 2024, Volume and Issue: 386(6720)

Published: Sept. 5, 2024

Age is a major risk factor for cancer, but how aging impacts tumor control remains unclear. In this study, we establish that of the immune system, regardless age stroma and tumor, drives lung cancer progression. Hematopoietic enhances emergency myelopoiesis, resulting in local accumulation myeloid progenitor–like cells tumors. These are source interleukin (IL)–1⍺, which enhanced response. The age-associated decline DNA methyltransferase 3A IL-1⍺ production, disrupting IL-1 receptor 1 signaling early during development normalized myelopoiesis slowed growth lung, colonic, pancreatic human tumors, identified an enrichment IL-1⍺–expressing monocyte-derived macrophages linked to age, poorer survival, recurrence, unraveling promotes offering actionable therapeutic strategies.

Language: Английский

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Mitochondrial DNA mutations drive aerobic glycolysis to enhance checkpoint blockade response in melanoma

Nature Cancer, Journal Year: 2024, Volume and Issue: 5(4), P. 659 - 672

Published: Jan. 29, 2024

The mitochondrial genome (mtDNA) encodes essential machinery for oxidative phosphorylation and metabolic homeostasis. Tumor mtDNA is among the most somatically mutated regions of cancer genome, but whether these mutations impact tumor biology debated. We engineered truncating mtDNA-encoded complex I gene, Mt-Nd5, into several murine models melanoma. These promoted a Warburg-like shift that reshaped microenvironments in both mice humans, consistently eliciting an anti-tumor immune response characterized by loss resident neutrophils. Tumors bearing were sensitized to checkpoint blockade neutrophil-dependent manner, with induction redox imbalance being sufficient induce this effect wild-type tumors. Patient lesions >50% mutation heteroplasmy demonstrated rate was improved ~2.5-fold over cancer. data nominate as functional regulators metabolism biology, potential therapeutic exploitation treatment stratification.

Language: Английский

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The multi-target mechanism of action of Selaginella doederleinii Hieron in the treatment of nasopharyngeal carcinoma: a network pharmacology and multi-omics analysis

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 2, 2025

Nasopharyngeal carcinoma (NPC) presents significant treatment challenges due to its complex etiology and late-stage diagnosis. The traditional Chinese medicine Selaginella doederleinii Hieron (S. doederleinii) has shown potentiality in NPC multi-target, multi-pathway anti-cancer mechanisms. First, we identified related target genes from databases like GeneCards, OMIM, DisGeNET, performed WGCNA analysis on the GSE53819 dataset identify several important gene modules NPC. Active components their targets S. were screened TCMSP other databases, identifying 32 overlapping genes. Gene Ontology (GO) Kyoto Encyclopedia of Genes Genomes (KEGG) pathway revealed that these are primarily involved critical biological processes protein phosphorylation cell cycle regulation. A protein–protein interaction network was constructed, cytoHubba six key (BCL2, MAPK14, ABCB1, PLK1, ATM, HMOX1). Kaplan–Meier immune infiltration further showed closely prognosis microenvironment patients. Single-cell RNA sequencing expression distribution across different types explored roles differentiation process malignant cells through pseudotime trajectory analysis. Molecular docking dynamics simulation results indicated Berberine-MAPK14 Matairesinol-PLK1 complexes have high binding affinity stability. Binding free energy calculations confirmed stability complexes. Based our comprehensive multi-level analysis, active may play a role multi-target synergistic effects.

Language: Английский

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Cytoprotective Role of Heme Oxygenase-1 in Cancer Chemoresistance: Focus on Antioxidant, Antiapoptotic, and Pro-Autophagy Properties

Antioxidants, Journal Year: 2023, Volume and Issue: 12(6), P. 1217 - 1217

Published: June 5, 2023

Chemoresistance remains the foremost challenge in cancer therapy. Targeting reactive oxygen species (ROS) manipulation is a promising strategy treatment since tumor cells present high levels of intracellular ROS, which makes them more vulnerable to further ROS elevation than normal cells. Nevertheless, dynamic redox evolution and adaptation are capable counteracting therapy-induced oxidative stress, leads chemoresistance. Hence, exploring cytoprotective mechanisms urgently needed overcome Heme oxygenase-1 (HO-1), rate-limiting enzyme heme degradation, acts as crucial antioxidant defense molecule response cellular stress. Recently, emerging evidence indicated that detoxification stress tolerance owing function HO-1 contribute chemoresistance various cancers. Enhanced expression or enzymatic activity was revealed promote apoptosis resistance activate protective autophagy, also involved development Moreover, inhibition multiple cancers identified reversing improving chemosensitivity. Here, we summarize most recent advances regarding antioxidant, antiapoptotic, pro-autophagy properties mediating chemoresistance, highlighting novel target for overcoming prognosis patients.

Language: Английский

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Heme: The Lord of the Iron Ring

Antioxidants, Journal Year: 2023, Volume and Issue: 12(5), P. 1074 - 1074

Published: May 10, 2023

Heme is an iron-protoporphyrin complex with essential physiologic function for all cells, especially those in which heme a key prosthetic group of proteins such as hemoglobin, myoglobin, and cytochromes the mitochondria. However, it also known that can participate pro-oxidant pro-inflammatory responses, leading to cytotoxicity various tissues organs kidney, brain, heart, liver, immune cells. Indeed, heme, released result tissue damage, stimulate local remote inflammatory reactions. These initiate innate responses that, if left uncontrolled, compound primary injuries promote organ failure. In contrast, cadre receptors are arrayed on plasma membrane designed either import into cell, or purpose activating specific signaling pathways. Thus, free serve deleterious molecule, one traffic highly cellular teleologically important survival. Herein, we review metabolism pathways, including synthesis, degradation, scavenging. We will focus trauma diseases, traumatic brain injury, trauma-related sepsis, cancer, cardiovascular diseases where current work suggests may be most important.

Language: Английский

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Strategies of Helicobacter pylori in evading host innate and adaptive immunity: insights and prospects for therapeutic targeting

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: Feb. 26, 2024

Helicobacter pylori ( H. ) is the predominant pathogen causing chronic gastric mucosal infections globally. During period from 2011 to 2022, global prevalence of infection was estimated at 43.1%, while in China, it slightly higher approximately 44.2%. Persistent colonization by can lead gastritis, peptic ulcers, and malignancies such as mucosa-associated lymphoid tissue (MALT) lymphomas adenocarcinomas. Despite eliciting robust immune responses host, thrives mucosa modulating host immunity, particularly altering functions innate adaptive cells, dampening inflammatory adverse its survival, posing challenges clinical management. The interaction between defenses intricate, involving evasion recognition modifying surface molecules, manipulating macrophage functionality, T cell evade surveillance. This review analyzes immunopathogenic mechanisms , underscoring importance identifying new therapeutic targets developing effective treatment strategies, discusses how development vaccines against offers hope for eradicating infections.

Language: Английский

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