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Review
. 2021 May 17;10(5):789.
doi: 10.3390/antiox10050789.

Clinical Significance of Heme Oxygenase 1 in Tumor Progression

Mariapaola Nitti  1 , Caterina Ivaldo  1 , Nicola Traverso  1 , Anna Lisa Furfaro  1
Affiliations
Review

Clinical Significance of Heme Oxygenase 1 in Tumor Progression

Mariapaola Nitti et al. Antioxidants (Basel). .

Abstract

Heme oxygenase 1 (HO-1) plays a key role in cell adaptation to stressors through the antioxidant, antiapoptotic, and anti-inflammatory properties of its metabolic products. For these reasons, in cancer cells, HO-1 can favor aggressiveness and resistance to therapies, leading to poor prognosis/outcome. Genetic polymorphisms of HO-1 promoter have been associated with an increased risk of cancer progression and a high degree of therapy failure. Moreover, evidence from cancer biopsies highlights the possible correlation between HO-1 expression, pathological features, and clinical outcome. Indeed, high levels of HO-1 in tumor specimens often correlate with reduced survival rates. Furthermore, HO-1 modulation has been proposed in order to improve the efficacy of antitumor therapies. However, contrasting evidence on the role of HO-1 in tumor biology has been reported. This review focuses on the role of HO-1 as a promising biomarker of cancer progression; understanding the correlation between HO-1 and clinical data might guide the therapeutic choice and improve the outcome of patients in terms of prognosis and life quality.

Keywords: HO-1; Nrf2; biomarker; cancer progression; patients; prognosis; therapy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of heme oxygenase 1 (HO-1) activity and regulation. HO-1 induction can be regulated at the transcriptional level by several stress-related transcription factors (Nrf2, AP-1, NF-kB, and HIF-1). Two polymorphisms that modify HO-1 inducibility have been indicated. Post-transcriptional regulation can involve miRNA. HO-1 regulates intracellular heme level catalyzing its degradation into biliverdin, carbon monoxide (CO), and ferrous iron (Fe2+). Biliverdin is converted into bilirubin by biliverdin reductase A (BVRA). Free iron activates iron transporters and induces the expression of ferritin. HO-1 metabolic products exert pro-survival activities, as indicated. A truncated form of HO-1, formed by signal peptide peptidase (SSP) cleavage, with nuclear localization and no enzymatic activity, has been described.
Figure 2
Figure 2
Schematic representation of the effects of HO-1 activation and generation of its metabolic products in healthy and cancer cells. HO-1 activation is involved in antioxidant defenses and in healthy cells promotes the hormetic response and cancer prevention through the generation of bilirubin and CO. In cancer cells, HO-1 favors cancer progression, and its inhibition represents a therapeutic opportunity. However, also HO-1 over-activation can be proposed as a therapeutic option, as it can favor unconventional ferroptosis through the accumulation of pro-oxidant-free iron.
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