A Dual Role of Heme Oxygenase-1 in Cancer Cells

International Journal of Molecular Sciences, Journal Year: 2018, Volume and Issue: 20(1), P. 39 - 39

Published: Dec. 21, 2018

Heme oxygenase (HO)-1 is known to metabolize heme into biliverdin/bilirubin, carbon monoxide, and ferrous iron, it has been suggested demonstrate cytoprotective effects against various stress-related conditions. HO-1 commonly regarded as a survival molecule, exerting an important role in cancer progression its inhibition considered beneficial number of cancers. However, increasing studies have shown dark side HO-1, which acts critical mediator ferroptosis induction plays causative factor for the several diseases. Ferroptosis newly identified iron- lipid peroxidation-dependent cell death. The metabolism makes candidate mediate protective or detrimental via induction. This review summarizes current understanding on regulatory mechanisms ferroptosis. amount cellular iron reactive oxygen species (ROS) determinative momentum excessive ROS tend enforce from perpetrator. Despite that related death, there prospective application therapy chemotherapeutic strategy tumors.

Language: Английский

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A review on heme oxygenase-1 induction: is it a necessary evil

Inflammation Research, Journal Year: 2018, Volume and Issue: 67(7), P. 579 - 588

Published: April 24, 2018

Language: Английский

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Mitochondria Targeting as an Effective Strategy for Cancer Therapy

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(9), P. 3363 - 3363

Published: May 9, 2020

Mitochondria are well known for their role in ATP production and biosynthesis of macromolecules. Importantly, increasing experimental evidence points to the roles mitochondrial bioenergetics, dynamics, signaling tumorigenesis. Recent studies have shown that many types cancer cells, including metastatic tumor therapy-resistant stem reliant on respiration, upregulate oxidative phosphorylation (OXPHOS) activity fuel Mitochondrial metabolism is crucial proliferation, survival, metastasis. OXPHOS dependency has been underlie development resistance chemotherapy radiotherapy. Furthermore, recent demonstrated elevated heme synthesis uptake leads intensified respiration generation, thereby promoting tumorigenic functions non-small cell lung (NSCLC) cells. Also, lowering uptake/synthesis inhibits effectively reduces oxygen consumption, inhibiting migration, growth NSCLC. Besides metabolic changes, dynamics such as fission fusion also altered These alterations render mitochondria a vulnerable target therapy. This review summarizes advances understanding cells contribute tumorigenesis drug resistance. It highlights novel approaches involving targeting

Language: Английский

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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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Heme Oxygenase 1 in the Nervous System: Does It Favor Neuronal Cell Survival or Induce Neurodegeneration?

International Journal of Molecular Sciences, Journal Year: 2018, Volume and Issue: 19(8), P. 2260 - 2260

Published: Aug. 1, 2018

Heme oxygenase 1 (HO-1) up-regulation is recognized as a pivotal mechanism of cell adaptation to stress. Under control different transcription factors but with prominent role played by Nrf2, HO-1 induction crucial also in nervous system response damage. However, several lines evidence have highlighted that expression associated neuronal damage and neurodegeneration especially Alzheimer’s Parkinson’s diseases. In this review, we summarize the current literature regarding pointing out molecular mechanisms possibly responsible for homeostasis neurodegeneration.

Language: Английский

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Crosstalk Between Oxidative Stress and Endoplasmic Reticulum (ER) Stress in Endothelial Dysfunction and Aberrant Angiogenesis Associated With Diabetes: A Focus on the Protective Roles of Heme Oxygenase (HO)-1

Frontiers in Physiology, Journal Year: 2019, Volume and Issue: 10

Published: Feb. 11, 2019

Type-2 diabetes prevalence is continuing to rise worldwide due physical inactivity and obesity epidemic. Diabetes fluctuations of blood sugar are related multiple micro- macrovascular complications, that attributed oxidative stress, endoplasmic reticulum (ER) activation inflammatory processes, which lead endothelial dysfunction characterized, among other features, by reduced availability nitric oxide (NO) aberrant angiogenic capacity. Several enzymatic anti-oxidant anti-inflammatory agents have been found play protective roles against stress its downstream signaling pathways. Of particular interest, heme oxygenase (HO) isoforms, specifically HO-1, attracted much attention as major cytoprotective players in conditions associated with inflammation stress. HO operates a key rate-limiting enzyme the process degradation iron-containing molecule, heme, yielding following byproducts: carbon monoxide (CO), iron, biliverdin. Because HO-1 induction was linked pro-oxidant states, it has regarded marker stress; however, accumulating evidence established metabolic cardiovascular disorders. The effects depend on several cellular mechanisms including generation bilirubin, an from heme; ferritin, strong chelator free iron; release CO, displays anti-apoptotic actions. current review article describes molecular contributing altered angiogenesis special focus interplay between ER response. summarizes hyperglycemia-induced discusses underlying effects.

Language: Английский

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The Multifaceted Role of Heme in Cancer

Frontiers in Oncology, Journal Year: 2020, Volume and Issue: 9

Published: Jan. 15, 2020

Heme, an iron-containing porphyrin, is of vital importance for cells due to its involvement in several biological processes, including oxygen transport, energy production and drug metabolism. Besides these functions, heme also bears toxic properties and, therefore, the amount inside must be tightly regulated. Similarly, intake from dietary sources strictly controlled meet body requirements. The multifaceted nature renders it a best candidate molecule exploited/controlled by tumor order modulate their energetic metabolism, interact with microenvironment sustain proliferation survival. present review summarizes literature on cancer, emphasizing consider as prominent player different aspects onset progression.

Language: Английский

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Heme catabolism by tumor-associated macrophages controls metastasis formation

Nature Immunology, Journal Year: 2021, Volume and Issue: 22(5), P. 595 - 606

Published: April 26, 2021

Language: Английский

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Betula etnensis Raf. (Betulaceae) Extract Induced HO-1 Expression and Ferroptosis Cell Death in Human Colon Cancer Cells

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(11), P. 2723 - 2723

Published: June 3, 2019

Betula etnensis Raf. (Birch Etna) belonging to the Betulaceae family grows on eastern slope of Etna. Many bioactive compounds present in species are considered promising anticancer agents. In this study, we evaluated effects B. bark methanolic extract a human colon cancer cell line (CaCo2). order elucidate mechanisms action extract, cellular redox status, cycle, and heme oxygenase-1 (HO-1) expression ferroptosis induction were evaluated. Cell viability proliferation tested by tetrazolium (MTT) assayand cycle analysis, while death was annexin V test lactic dehydrogenase (LDH) release. Cellular status assessed measuring thiol groups (RSH) content, reactive oxygen (ROS) production, lipid hydroperoxide (LOOH) levels (γ-glutamylcysteine synthetase) γ-GCS HO-1 expressions. The significantly reduced CaCo2, inducing necrotic concentration-depending manner. addition, an increase ROS decrease RSH content without modulation detected, with augmentation LOOH drastic expression. These results suggest that promotes oxidative microenvironment resulting CaCo2 mediated hyper-expression.

Language: Английский

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