Heme Oxygenase-1 and Carbon Monoxide Regulate Growth and Progression in Glioblastoma Cells

Castracani, Carlo Castruccio; Longhitano, Lucia; Distefano, Alfio; Rosa, Michelino Di; Pittalà, Valeria; Lupo, Gabriella; Caruso, Massimo; Corona, Daniela; Tibullo, Daniele; Volti, Giovanni Li

doi:10.1007/s12035-020-01869-7

Cited by 27 publications

(15 citation statements)

References 55 publications

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“…We choose these cell lines since the associated cancers overexpress HO-1 protein, and their treatment still represents an unmet clinical need. 6 , 8 , 10 As clearly shown in Figure 8 , panels A and B, HO-1 levels are significantly higher in U87MG when compared to those of the others. These data were confirmed by immunofluorescence analysis assessing HO-1 immunoreactivity (green fluorescence) in all cell lines under basal conditions ( Figure 8 C).…”

Section: Resultsmentioning

confidence: 61%

Discovery of Novel Acetamide-Based Heme Oxygenase-1 Inhibitors with Potent In Vitro Antiproliferative Activity

et al. 2021

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Heme oxygenase-1 (HO-1) promotes heme catabolism exercising cytoprotective roles in normal and cancer cells. Herein, we report the design, synthesis, molecular modeling, and biological evaluation of novel HO-1 inhibitors. Specifically, an amide linker in the central spacer and an imidazole were fixed, and the hydrophobic moiety required by the pharmacophore was largely modified. In many tumors, overexpression of HO-1 correlates with poor prognosis and chemoresistance, suggesting the inhibition of HO-1 as a possible antitumor strategy. Accordingly, compounds 7i and 7l – p emerged for their potency against HO-1 and were investigated for their anticancer activity against prostate (DU145), lung (A549), and glioblastoma (U87MG, A172) cancer cells. The selected compounds showed the best activity toward U87MG cells. Compound 7l was further investigated for its in-cell enzymatic HO-1 activity, expression levels, and effects on cell invasion and vascular endothelial growth factor (VEGF) extracellular release. The obtained data suggest that 7l can reduce cell invasivity acting through modulation of HO-1 expression.

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Section: Resultsmentioning

confidence: 61%

Discovery of Novel Acetamide-Based Heme Oxygenase-1 Inhibitors with Potent In Vitro Antiproliferative Activity

et al. 2021

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“…Tumor cells are capable of adopting a more motile mesenchymal-like phenotype, referred to as epithelial to mesenchymal transition (EMT), which facilitates the metastatic potential of the cells. In a model of human glioma, CO was demonstrated to be capable of increasing tumor cell migration ( 165 ). There is also direct evidence that HO-1 activity can contribute to EMT ( 166 ).…”

Section: Ho-1 In Metastasismentioning

confidence: 99%

The Diverse Roles of Heme Oxygenase-1 in Tumor Progression

2021

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Heme oxygenase-1 (HO-1) is an inducible intracellular enzyme that is expressed in response to a variety of stimuli to degrade heme, which generates the biologically active catabolites carbon monoxide (CO), biliverdin and ferrous iron (Fe2+). HO-1 is expressed across a range of cancers and has been demonstrated to promote tumor progression through a variety of mechanisms. HO-1 can be expressed in a variety of cells within the tumor microenvironment (TME), including both the malignant tumor cells as well as stromal cell populations such as macrophages, dendritic cells and regulatory T-cells. Intrinsically to the cell, HO-1 activity provides antioxidant, anti-apoptotic and cytoprotective effects via its catabolites as well as clearing toxic intracellular heme. However, the catabolites of heme degradation can also diffuse outside of the cell to extrinsically modulate the wider TME, influencing cellular functionality and biological processes which promote tumor progression, such as facilitating angiogenesis and metastasis, as well as promoting anti-inflammation and immune suppression. Pharmacological inhibition of HO-1 has been demonstrated to be a promising therapeutic approach to promote anti-tumor immune responses and inhibit metastasis. However, these biological functions might be context, TME and cell type-dependent as there is also conflicting reports for HO-1 activity facilitating anti-tumoral processes. This review will consider our current understanding of the role of HO-1 in cancer progression and as a therapeutic target in cancer.

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“…The analysis of the microarray dataset from clinical biopsies showed that HMOX1 expression levels significantly increase in glioma grade IV brain biopsies when compared to grade I, II, and III. Additionally, the expression level of HO-1 in glioma grade IV brain biopsies was correlated to the chemotaxis gene expression [ 110 ]. In A2780 and SKOV-3 ovarian cancer cells, ROS scavengers, namely N -acetyl- L -cysteine and HO-1 inhibitor ZnPP, were shown to relieve ROS production and autophagy, and ameliorate cell migration and invasion by reversing the epithelial–mesenchymal transition [ 111 ].…”

Section: The Contradictory Role Of Ho-1 In Tumorigenesismentioning

confidence: 99%

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

Chiang

Chen

Chang

2021

Cells

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

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Heme Oxygenase-1 and Carbon Monoxide Regulate Growth and Progression in Glioblastoma Cells

Cited by 27 publications

References 55 publications

Discovery of Novel Acetamide-Based Heme Oxygenase-1 Inhibitors with Potent In Vitro Antiproliferative Activity

Discovery of Novel Acetamide-Based Heme Oxygenase-1 Inhibitors with Potent In Vitro Antiproliferative Activity

The Diverse Roles of Heme Oxygenase-1 in Tumor Progression

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

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