Abstract
Haem oxygenase-1 (HO-1) catalyses the rate-limiting step in haem degradation. All three metabolites resulting from haem degradation (carbon monoxide (CO), biliverdin and free iron) have anti-inflammatory and anti-apoptotic properties. HO-1 is a stress-inducible enzyme found extensively expressed in a vast variety of both human and murine cancers, where it serves as an essential survival molecule by modulating expression of molecules regulating apoptosis and stimulating angiogenesis. In addition, HO-1 contributes in a critical manner to inhibition or termination of inflammation. Consequently, several anticancer strategies aim at targeting HO-1. The inhibition of HO-1 may cause tumour cells to become more sensitive to chemotherapy and radiation therapy. The water-soluble forms of the HO-1 inhibitor Zinc protoporphyrin (ZnPP) have seemed promising in different in-vivo models, in which it has induced growth arrest in tumour cells with few, if any, side effects. Studies have suggested that HO-1 may also function to disrupt the tumour metastasising process, since the expression of the metalloprotease MMP9 is inversely correlated with HO-1 expression.
Additionally, HO-1 has anti-inflammatory functions which play a very important role in the negative regulation of the immune system. Immunological targeting of HO-1 might represent an interesting approach, as epitopes derived from HO- 1 have been found exclusively on tumour tissue. Natural HO-1-specific T-cell responses have been identified in cancer patients. Hence, recently HO-1-specific, CD8+ regulatory T cells were described in cancer patients, which in concert with HO-1 expression might be responsible for a highly immunosuppressive tumour microenvironment.
Here, we summarise current knowledge of the role of HO-1 in cancer, report the different results of the targeting of HO-1 in preclinical and clinical settings, and discuss future opportunities.
Keywords: Cancer, haem oxygenase-1, regulatory T cells, tumour immunology, zinc protoporphyrin.
Current Cancer Drug Targets
Title:The Expression, Function and Targeting of Haem Oxygenase-1 in Cancer
Volume: 14 Issue: 4
Author(s): Mads Duus Hjortso and Mads Hald Andersen
Affiliation:
Keywords: Cancer, haem oxygenase-1, regulatory T cells, tumour immunology, zinc protoporphyrin.
Abstract: Haem oxygenase-1 (HO-1) catalyses the rate-limiting step in haem degradation. All three metabolites resulting from haem degradation (carbon monoxide (CO), biliverdin and free iron) have anti-inflammatory and anti-apoptotic properties. HO-1 is a stress-inducible enzyme found extensively expressed in a vast variety of both human and murine cancers, where it serves as an essential survival molecule by modulating expression of molecules regulating apoptosis and stimulating angiogenesis. In addition, HO-1 contributes in a critical manner to inhibition or termination of inflammation. Consequently, several anticancer strategies aim at targeting HO-1. The inhibition of HO-1 may cause tumour cells to become more sensitive to chemotherapy and radiation therapy. The water-soluble forms of the HO-1 inhibitor Zinc protoporphyrin (ZnPP) have seemed promising in different in-vivo models, in which it has induced growth arrest in tumour cells with few, if any, side effects. Studies have suggested that HO-1 may also function to disrupt the tumour metastasising process, since the expression of the metalloprotease MMP9 is inversely correlated with HO-1 expression.
Additionally, HO-1 has anti-inflammatory functions which play a very important role in the negative regulation of the immune system. Immunological targeting of HO-1 might represent an interesting approach, as epitopes derived from HO- 1 have been found exclusively on tumour tissue. Natural HO-1-specific T-cell responses have been identified in cancer patients. Hence, recently HO-1-specific, CD8+ regulatory T cells were described in cancer patients, which in concert with HO-1 expression might be responsible for a highly immunosuppressive tumour microenvironment.
Here, we summarise current knowledge of the role of HO-1 in cancer, report the different results of the targeting of HO-1 in preclinical and clinical settings, and discuss future opportunities.
Export Options
About this article
Cite this article as:
Hjortso Duus Mads and Andersen Hald Mads, The Expression, Function and Targeting of Haem Oxygenase-1 in Cancer, Current Cancer Drug Targets 2014; 14 (4) . https://dx.doi.org/10.2174/1568009614666140320111306
DOI https://dx.doi.org/10.2174/1568009614666140320111306 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
The Interaction of Histone Deacetylase Inhibitors and DNA Methyltransferase Inhibitors in the Treatment of Human Cancer Cells
Current Medicinal Chemistry - Anti-Cancer Agents Cancer/Testis Antigens Trigger Epithelial-Mesenchymal Transition and Genesis of Cancer Stem-Like Cells
Current Pharmaceutical Design Newer Avenues for the Treatment of Leptomeningeal Carcinomatosis
Central Nervous System Agents in Medicinal Chemistry Natural Plant Extracts as Potential Therapeutic Agents for the Treatment of Cancer
Current Topics in Medicinal Chemistry Role of the Cannabinoid System in Pain Control and Therapeutic Implications for the Management of Acute and Chronic Pain Episodes
Current Neuropharmacology Neuroinflammation: A Therapeutic Target of Cotinine for the Treatment of Psychiatric Disorders?
Current Pharmaceutical Design Glioblastoma Targeted Gene Therapy Based on pEGFP/p53-Loaded Superparamagnetic Iron Oxide Nanoparticles
Current Gene Therapy Natural and Engineered Cystine Knot Miniproteins for Diagnostic and Therapeutic Applications
Current Pharmaceutical Design Molecular Biology, Pharmacology and Functional Role of the Plasma Membrane Dopamine Transporter
CNS & Neurological Disorders - Drug Targets Possible Binding Mode Analysis of Pyrazolo-triazole Hybrids as Potential Anticancer Agents through Validated Molecular Docking and 3D-QSAR Modeling Approaches
Letters in Drug Design & Discovery A Systems Biology Road Map for the Discovery of Drugs Targeting Cancer Cell Metabolism
Current Pharmaceutical Design cAMP-Mediated Regulation of CYP Enzymes and Its Application in Chemotherapy
Drug Metabolism Letters Editorial (Thematic Issue: New Trends in Pharmaceutical Nanotechnology)
Current Pharmaceutical Design Recent Advances in the Synthesis and Anticancer Activity of Some Molecules Other Than Nitrogen Containing Heterocyclic Moeities
Mini-Reviews in Medicinal Chemistry 2´,3´-Dialdehyde of ATP, ADP, and Adenosine Inhibit HIV-1 Reverse Transcriptase and HIV-1 Replication
Current HIV Research Innovative Cancer Treatments that Augment Radiotherapy or Chemotherapy by the Use of Immunotherapy or Gene Therapy
Recent Patents on Anti-Cancer Drug Discovery Synergism of Temozolomide, Metformin, and Epigallocatechin Gallate Promotes Oxidative Stress-Induced Apoptosis in Glioma Cells
Current Drug Therapy Targeting Malignancies with Disulfiram (Antabuse): Multidrug Resistance, Angiogenesis, and Proteasome
Current Cancer Drug Targets 5-HT3 Receptors
Current Drug Targets - CNS & Neurological Disorders miR-15b and miR-21 as Circulating Biomarkers for Diagnosis of Glioma
Current Genomics