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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 bee...
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... date, the most consistent data regarding the correlation among HO-1 expression, cancer progression, patient prognosis, and outcome derive from immunohistochemistry studies on specimens from surgical patients. The data available in the literature are synthesized in Table 1 at the end of this paragraph. It is important to underline that, since Nrf2 is crucially involved in the regulation of HO-1 transcription, its expression has been considered as well. ...Similar publications
A competitividade regional, dada pela capacidade das regiões em gerar riquezas e revertê-la como melhoria da qualidade de vida para seus habitantes, é amplamente discutida por acadêmicos e decisores políticos. O artigo buscou aprofundar-se em como mensurar e classificar a competitividade regional em municípios brasileiros? Foi utilizada uma adaptaç...
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... Fisetin also demonstrated protective effects against DNA damage in gamma-radiation-exposed Chinese hamster lung fibroblasts by reducing intracellular levels of reactive oxygen species, thereby preventing DNA damage, lipid peroxidation, and protein damage [55]. The enzyme heme-oxygenase-1 (HO-1) is important for cellular stress adaptation and prevention of carcinogenesis due to the anti-apoptotic, antioxidant, and anti-inflammatory properties of its metabolites. ...
... The enzyme heme-oxygenase-1 (HO-1) is important for cellular stress adaptation and prevention of carcinogenesis due to the anti-apoptotic, antioxidant, and anti-inflammatory properties of its metabolites. However, HO-1 is also implicated in cancer development and progression, with its expression correlating with tumor growth, metastasis, angiogenesis, drug resistance, and poor prognosis in a tissue-specific manner [55]. Fisetin has been found to induce the expression of the cytoprotective enzyme HO-1 in endothelial cells from human umbilical veins [62]. ...
Cancer remains a leading cause of mortality globally, characterized by the uncontrolled proliferation of abnormal cells, invasion of healthy tissues, and potential metastasis. Natural compounds have become a focus in cancer research due to their potential therapeutic roles. Among these, fisetin, a dietary flavonoid, demonstrates notable anti-cancer properties through various molecular mechanisms. This review evaluates the chemoprotective and chemotherapeutic potential of fisetin, focusing on its mechanisms of action against cancer and its capacity to enhance cancer treatment. A systematic literature search was conducted across PubMed, Web of Science, and Scopus databases using keywords related to fisetin and cancer. The review synthesizes findings from in vitro and in vivo studies examining fisetin’s effects on signaling pathways, apoptosis induction, oxidative stress modulation, and synergistic potential with chemotherapeutic agents. Fisetin has shown the ability to suppress tumor growth and metastasis by modulating critical signaling pathways, including PI3K/Akt/mTOR, NF-κB, and MAPK. It induces apoptosis in cancer cells through mitochondrial and endoplasmic reticulum stress responses and demonstrates antioxidative properties by reducing reactive oxygen species. Additionally, fisetin enhances the efficacy of conventional chemotherapies, indicating its role as a potential adjuvant in cancer treatment. Fisetin presents a promising natural compound with diverse anti-cancer effects, impacting cell cycle arrest, apoptosis, and oxidative stress pathways. Further clinical studies are warranted to fully elucidate its therapeutic potential and to optimize its delivery for improved bioavailability in cancer patients.
... The overexpression is commonly seen in a wide range of cancer types to favor their survival, proliferation, invasion, metastasis, resistance to anticancer therapy, and modulating tumor microenvironment. 3 Notably, HO-1 expression level is positively related to the disease stage and poor prognosis. 4 Therefore, it holds the potential to serve as a biomarker for not only cancer diagnosis but also cancer prognosis and treatment monitoring. ...
Heme oxygenase-1 (HO-1) catalyzes heme degradation on the consumption of NADPH and molecular oxygen. As an inducible enzyme, HO-1 is highly induced in various disease states, including cancer. Currently, two fluorescent probes for HO-1 have been designed based on the catalytic activity of HO-1, in which the probes serve as a substrate, so NADPH is required to enable the detection. Probes functioning in a NADPH-dependent way may influence other NADPH-consuming pathways, as all these pathways share a common NADPH pool. Here, we report the peptide-based fluorescent probe NBD-P5 as a simple alternative approach for HO-1 sensing. The designed probe NBD-P5 functions independently of the catalytic activity of HO-1, therefore enabling fast and sensitive detection of HO-1 with no requirements of other substances, including NADPH and biliverdin reductase. Moreover, it overcomes the need for a large substrate amount and long incubation time during the detection. NBD-P5 can be quickly taken up by cells, demonstrates an excellent colocalization with the endoplasmic reticulum (where HO-1 is mainly located), and is shown to be reliable in reporting changes in HO-1 levels in live cells. This work provides a simple alternative approach for designing HO-1 fluorescent probes, and we expect it will act as a practical tool for further studying HO-1 biology.
... Transcription of downstream genes like HO-1, NQO1, GCLM, and GCLC was initiated when the NRF2 combines with MAF and ARE in the nucleus [12]. Among these, HO1 and MDM2 are associated with cancer progression [15,16]. HO1 is reported to be elevated in various tumor cell types, including hepatoma, gastric cancer, lung cancer, and breast cancer, and it stimulates rapid cell growth, promotes angiogenesis, and aids in tumor metastasis [17]. ...
Background: Retinoblastoma is a rare intraocular malignancy that leads to vision loss in children. While copper (Cu) chelation has been reported as a therapy in many cancers, its relevance to retinoblastoma has not yet been explored. Objectives: In this study, we have explored the role of penicillamine (a Cu chelator) as a therapeutic target for retinoblastoma using Y79 cells as a model. Methods: The effect of the Cu chelator on the viability of Y79 was assessed using the MTT assay. Additionally, we performed nuclear fractionation to assess Nuclear factor erythroid 2–related factor 2 (NRF2) activation, evaluated the downstream targets of NRF2 at transcript and protein levels, and measured SOD (superoxide dismutase) activity. Results: Penicillamine (2 mM) induced cell death in Y79 cells, inhibited NRF2 signaling, and reduced SOD activity. Furthermore, the downstream targets of NRF2 namely VEGF as well as PCNA (proliferating cell nuclear antigen) were decreased with penicillamine, which induced cell death in Y79 cells. We observed similar results in HeLa cells (positive control) comparable to Y79 cells. Conclusion: Therefore, we speculate that penicillamine could be a target for retinoblastoma as it induces cell death in Y79 cells by regulating NRF2 nuclear translocation and decreasing its downstream targets.
... Overexpression of HMOX1 can protect HepG-2 cells from the antitumor effects of cisplatin and simultaneously inhibit HCC progression through microRNA pathways [28]. The interactions between HMOX1 and various microRNAs reveal a complex regulatory network [29]. Furthermore, while our study indicates a correlation between elevated HMOX1 expression and [24]. ...
Most oncogenic genes contribute to cancer progression, but their role and regulatory mechanisms are not yet fully understood in hepatocellular carcinoma (HCC). This study aimed to explore the role of miR-328-3p and the regulatory relationship between miR-328-3p and HMOX1 in HCC.
We utilized Cox and LASSO regression to identify a panel of oncogenic genes associated with hepatocellular carcinoma (HCC) progression within the TCGA-LIHC cohort and the GSE104580 dataset. The expression levels of the hub gene, HMOX1, were assessed in HCC cell lines using qPCR. The functional roles of miR-328-3p and HMOX1 were evaluated through a series of in vitro assays, including CCK-8 for proliferation, colony formation, wound healing, and Transwell assays for migration and invasion. The direct interaction between miR-328-3p and HMOX1 was explored using a luciferase reporter assay, Western blot (WB) for protein expression analysis, and functional assays to determine the impact on cell proliferation and migration.
Eight candidate genes (BIRC5, TNSF4, SPP1, HMOX1, ADM, RBP2, IGF1, and LECT2) were screen out. The hub gene HMOX1 among had high expression level in HCC cell lines. High HMOX1 expressing cell line had significantly increased proliferation and migration capacities. Moreover, HMOX1 was identified as a target of miR-328-3p, which regulated the HMOX1 expression in qPCR and WB assays. High miR-328-3p expressing HCC cell had diminished capacities for proliferation and migration. However, concurrent upregulation of HMOX1 expression resulted in enhanced proliferative and migratory abilities in these cells.
Our study has advanced our understanding of the roles of miR-328-3p and HMOX1 in HCC, demonstrating the inhibitory effect of miR-328-3p on the oncogenic activity of HMOX1. Hence, these results revealed the function of miR-328-3p and a novel mechanistic pathway for HCC and suggested the potential therapeutic targeting of miR-328-3p and HMOX1 for HCC intervention strategies.
... Biliverdin is subsequently converted to bilirubin by biliverdin reductase, which scavenges or neutralizes ROS, thus mitigating oxidative stress. 82, 92 As a gaseous signaling molecule, CO exerts various effects in signal transduction, including vasodilation, anti-inflammatory responses, anti-apoptotic effects, and the promotion of angiogenesis. 93 Additionally, the activation of HO-1 upregulates the expression of ferritin, which binds ferrous iron, thereby reducing oxidative stress 94 ( Figure 2). ...
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a progressive liver disorder with a rising prevalence. It begins with lipid accumulation in hepatocytes and gradually progresses to Metabolic-associated steatohepatitis (MASH), fibrosis, cirrhosis, and potentially hepatocellular carcinoma (HCC). The pathophysiology of MASLD is complex and involves multiple factors, with oxidative stress playing a crucial role. Oxidative stress drives the progression of MASLD by causing cellular damage, inflammatory responses, and fibrosis, making it a key pathogenic mechanism. The Nuclear Factor Erythroid 2-Related Factor 2 / Heme Oxygenase-1 (Nrf2/HO-1) signaling axis provides robust multi-organ protection against a spectrum of endogenous and exogenous insults, particularly oxidative stress. It plays a pivotal role in mediating antioxidant, anti-inflammatory, and anti-apoptotic responses. Many studies indicate that activating the Nrf2/HO-1 signaling pathway can significantly mitigate the progression of MASLD. This article examines the role of the Nrf2/HO-1 signaling pathway in MASLD and highlights natural compounds that protect against MASLD by targeting Nrf2/HO-1 activation. The findings indicate that the Nrf2/HO-1 signaling pathway holds great promise as a therapeutic target for MASLD.
... HO-1 is traditionally recognized for its role in haem degradation and involvement in diverse inflammatory processes (5). Serving as a stress-induced protein, HO-1 is increased in response to oxidative stress (6). ...
Objectives:
This study explores the early identification of rheumatoid arthritis (RA) patients at elevated risk of progression. Haem-oxygenase-1 (HO-1) is a marker of oxidative stress in inflammation. Here, we investigate HO-1 as a biomarker of oxidative stress and its association with clinical disease activity and radiographic progression in RA.
Method:
Baseline HO-1 was measured sequentially in plasma samples from patients with early rheumatoid arthritis (eRA) (n = 80). Disease Activity Score based on 28-joint count-C-reactive protein, Clinical Disease Activity Index, and total Sharp score were used to evaluate the disease course serially over 2 years. Paired plasma and synovial fluid samples were examined for HO-1 in active established rheumatoid arthritis (esRA) (n = 20). Plasma from healthy control subjects was also included (n = 35).
Results:
Plasma HO-1 levels were increased in eRA {1373 pg/mL [interquartile range (IQR) 1110-2050]} and esRA [2034 pg/mL (IQR 1630-2923)] compared with controls [1064 pg/mL (IQR 869.5-1378)]. HO-1 plasma levels decreased with treatment. Baseline HO-1 correlated with disease activity and radiographic progression. A strong, linear correlation was found between synovial and plasma HO-1 levels (r = 0.75, p < 0.001).
Conclusion:
In eRA, plasma levels of HO-1 were increased and correlated with disease and radiographic progression. A baseline measurement of plasma HO-1 levels demonstrated superior performance to currently used clinical and serological disease markers in the prediction of radiographic progression. Plasma HO-1 may function as a first-in-class biomarker of synovial oxidative stress in RA.
... In pancreatitis, HO-1 upregulation in macrophages is part of the process required for the resolution of inflammation [43,44,74,75]. However, increased HO-1 expression (Figure 1) is correlated with cancer progression and with poor prognosis in pancreatic cancer [44,[76][77][78]. We hypothesized that Kras mutations in epithelial cells disrupt the normal regulation of HO-1 in macrophages to resolve inflammation in pancreatitis, thereby prolonging HO-1 overexpression and therefore contributing to disease progression. ...
In pancreatic cancer, the tumor microenvironment (TME) accounts for up to 90% of the tumor mass. Pancreatitis, characterized by the increased infiltration of macrophages into the pancreas, is a known risk factor for pancreatic cancer. The NRF2 (nuclear factor erythroid 2-related factor 2) transcription factor regulates responses to oxidative stress and can promote cancer and chemoresistance. NRF2 also attenuates inflammation through the regulation of macrophage-specific genes. Heme oxygenase 1 (HO-1) is expressed by anti-inflammatory macrophages to degrade heme, and its expression is dependent on NRF2 translocation to the nucleus. In macrophages stimulated with conditioned media from pancreatic cancer cells, HO-1 protein levels increased, which correlated with higher NRF2 expression in the nuclear fraction. Significant differences in macrophage infiltration and HO-1 expression were detected in LSL-KrasG12D/+; Pdx-1-Cre (KC) mice, Nrf2 whole-body knockout (KO) mice and wildtype mice with pancreatitis. Since epigenetic modulation is a mechanism used by tumors to regulate the TME, using small molecules as epigenetic modulators to activate immune recognition is therapeutically desirable. When the bromodomain inhibitor I-BET-762 was used to treat macrophages or mice with pancreatitis, high levels of HO-1 were reduced. This study shows that bromodomain inhibitors can be used to prevent physiological responses to inflammation that promote tumorigenesis.
... cancer development and therapeutic failure because HO-1 accelerates the production of tumor neovasculature and confers a selective advantage in overcoming increased oxidative stress during carcinogenesis and therapy to tumor cells [178]. Several studies have suggested that HO-1 is involved in tumor induction and can promote tumor growth and metastasis more effectively through catabolites. ...
Reactive oxygen species are involved in the pathogenesis of cancers and metabolic diseases, including diabetes, obesity, and fatty liver disease. Thus, inhibiting the generation of free radicals is a promising strategy to control the onset of metabolic diseases and cancer progression. Various synthetic drugs and natural product-derived compounds that exhibit antioxidant activity have been reported to have a protective effect against a range of metabolic diseases and cancer. This review highlights the development and aggravation of cancer and metabolic diseases due to the imbalance between pro-oxidants and endogenous antioxidant molecules. In addition, we discuss the function of proteins that regulate the production of reactive oxygen species as a strategy to treat metabolic diseases. In particular, we summarize the role of proteins such as nuclear factor-like 2, Sestrin, and heme oxygenase-1, which regulate the expression of various antioxidant genes in metabolic diseases and cancer. We have included recent literature to discuss the latest research on identifying novel signals of antioxidant genes that can control metabolic diseases and cancer.
... HO-1 is a stress-inducible enzyme that is regarded as an antioxidant and cytoprotective agent. The presence of high levels of HO-1 in tumour cells is typically associated with a reduction in survival (Nitti et al., 2021). The results of the study indicate that CUDC-101 also targets HO-1 and upregulates its expression in six EGFR mutant cell lines (Figs. 7 and 8). ...
The epidermal growth factor receptor (EGFR) represents an effective target for the treatment of non-small cell lung cancer. In the treatment of classical EGFR mutations, EGFR tyrosine kinase inhibitors have achieved desirable clinical efficacy. However, the effectiveness of tyrosine kinase inhibitors (TKIs) against the L861Q mutation has not been fully established. In this study, the four cell lines containing the L861Q mutation were constructed by CRISPR and the anti-tumour effects of CUDC-101 on them were investigated in vitro by various chemosensitivity methods, with afatinib serving as a positive control. The results demonstrated that CUDC-101 inhibited the proliferation and clonogenic capacity on the four cells through the ERK or AKT pathways, decreased the mitochondrial membrane potential of the cells, blocked the cell cycle and promoted apoptosis. Our findings suggest that CUDC-101 may be a promising treatment option for NSCLC patients with the EGFR exon 18 substitution mutation L861Q.
... Interestingly, XL-888 treatment led to an upregulation in the expression of hypoxia signalingrelated genes HMOX1 and SLC2A1, whereas Debio0932 treatment resulted in a downregulation of CA9 and HMOX1 expression. Overexpression of HMOX1 has been identified in a variety of cancers and is linked to immune evasion, angiogenesis, cancer cell proliferation, invasion, and treatment resistance [50]. SLC2A1 encodes GLUT1, a glucose transporter involved in the metabolism of glucose, which provides an energy source for cell proliferation and contributes to cancer progression and development [51]. ...
Neuroblastoma is a common nervous system tumor in childhood, and current treatments are not adequate. HSP90 is a molecular chaperone protein that plays a critical role in the regulation of cancer-related proteins. HSP90 inhibition may exert anticancer effects by targeting cancer-related processes such as tumor growth, cell proliferation, metastasis, and apoptosis. Therefore, HSP90 inhibition is a promising strategy in the treatment of various types of cancer, and the development of next-generation inhibitors could potentially lead to more effective and safer treatments. XL-888 and Debio0932 is a next-generation HSP90 inhibitor and can inhibit the correct folding and stabilization of client proteins that cancer-associated HSP90 helps to fold correctly. In this study, we aimed to investigate the comprehensive molecular pathways of the anticancer activity of XL-888 and Debio0932 in human neuroblastoma cells SH-SY5Y. The cytotoxic effects of XL-888 and Debio0932 on the neuroblastoma cell line SH-SY5Y cells were evaluated by MTT assay. Then, the effect of these HSP90 inhibitors on the expression of important genes in cancer was revealed by Quantitative Real Time Polymerase Chain Reaction (qRT-PCR) method. The qRT-PCR data were evaluated using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) biological process tools. Finally, the effect of HSP90 inhibitors on HSP27, HSP70 and HSP90 protein expression was investigated by Western blotting analysis. The results revealed that XL-888 and Debio0932 had a role in regulating many cancer-related pathways such as migration, invasion, metastasis, angiogenesis, and apoptosis in SH-SY5Y cells. In conclusion, it shows that HSP90 inhibitors can be considered as a promising candidate in the treatment of neuroblastoma and resistance to chemotherapy.
