Dual role of heme iron in cancer; promotor of carcinogenesis and an inducer of tumour suppression
| Autor: | Katherine Ting-Wei Lee, Vinod Gopalan, D. Lakal O. Dissabandara, S. M. K. Gamage, Alfred King-Yin Lam |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Programmed cell death Carcinogenesis NF-E2-Related Factor 2 Iron Clinical Biochemistry Cell Inflammation Heme medicine.disease_cause Pathology and Forensic Medicine 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Neoplasms medicine Humans Inducer Molecular Biology Carcinogen chemistry.chemical_classification Reactive oxygen species Chemistry 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Cancer research Tumor Suppressor Protein p53 medicine.symptom Heme Oxygenase-1 |
| Zdroj: | Experimental and Molecular Pathology. 120:104642 |
| ISSN: | 0014-4800 |
| DOI: | 10.1016/j.yexmp.2021.104642 |
| Popis: | Purpose Heme is a crucial compound for cell survival but is also equipped with the potential to be toxic and carcinogenic to cells. However, with the recent advancement of knowledge regarding ferroptosis, the iron mediated cell death, heme can be postulated to induce tumour suppression through ferroptosis. This review summarizes the literature on the carcinogenic and anticarcinogenic properties of heme with specific emphasis on the alterations observed on heme synthesis, metabolism and transport in tumour cells. Methods Literature search was performed in PubMed data base using the MeSH terms ‘heme iron or heme’, ‘cancer or carcinogenesis’ and ‘tumour suppression’ or ‘anticarcinogenic properties. Out of 189 results, 166 were relevant to the current review. Results Heme supports carcinogenesis via modulation of immune cell function, promoting inflammation and gut dysbiosis, impeding tumour suppressive potential of P53 gene, promoting cellular cytotoxicity and reactive oxygen species generation and modulating Nfr2 /HO-1 axis. The carcinogenic and anticarcinogenic properties of heme are both dose and oxygen concentration dependant. At low doses, heme is harmless and even helpful in maintaining the much-needed redox balance within the cell. However, when heme exceeds physiological concentrations, it could initiate and propagate carcinogenesis, due to its ability to produce reactive oxygen species (ROS). The same phenomenon of heme mediated ROS generation could be manipulated to initiate tumour suppression via ferroptosis, but the therapeutic doses are yet to be determined. Conclusion Heme iron possesses powerful carcinogenic and anticarcinogenic properties which are dosage and oxygen availability dependant. |
| Databáze: | OpenAIRE |
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