Histamine: a potential cytoprotective agent to improve cancer therapy?

Lamas, Diego José Martinel; Nicoud, Melisa Beatriz; Sterle, Helena Andrea; Cremaschi, Graciela; Medina, Vanina Araceli

doi:10.1038/cddis.2015.378

Cited by 19 publications

(18 citation statements)

References 14 publications

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“…Histamine is derived from the decarboxylation of histidine, which is exclusively catalyzed by HDC (36). There is growing evidence suggesting that histamine is directly involved in carcinogenesis and may serve as a potential cytoprotective agent to improve cancer therapy (37). According to some investigators, histamine-based therapies facilitate DNA damage, apoptosis, and senescence in carcinoma cells and remarkably increase the survival of tumor-bearing animals (38).…”

Section: Resultsmentioning

confidence: 99%

Spatially resolved metabolomics to discover tumor-associated metabolic alterations

Sun

Song

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

271

189

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SignificanceTumor cells reprogram their metabolism to support cell growth, proliferation, and differentiation, thus driving cancer progression. Profiling of the metabolic signatures in heterogeneous tumors facilitates the understanding of tumor metabolism and introduces potential metabolic vulnerabilities that might be targeted therapeutically. We proposed a spatially resolved metabolomics method for high-throughput discovery of tumor-associated metabolite and enzyme alterations using ambient mass spectrometry imaging. Metabolic pathway-related metabolites and metabolic enzymes that are associated with tumor metabolism were efficiently discovered and visualized in heterogeneous esophageal cancer tissues. Spatially resolved metabolic alterations hold the key to defining the dependencies of metabolism that are most limiting for cancer growth and exploring metabolic targeted strategies for better cancer treatment.

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Section: Resultsmentioning

confidence: 99%

Spatially resolved metabolomics to discover tumor-associated metabolic alterations

Sun

Song

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

271

189

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“…In the same model, histamine administration was demonstrated to potentiate ionizing radiation and doxorubicin therapies (Martinel Lamas et al, 2015a,b,d).…”

Section: H4r Expression In Gynecological and Breast Cancermentioning

confidence: 97%

“…All the studies, using different H4R ligands and also genetic down-regulation of H4R, demonstrated that the principal receptor subtype involved in the histamine-induced reduction of proliferation was the H4R (Medina et al, 2008; Martinel Lamas et al, 2013). The in vivo administration of histamine or H4R agonists (e.g., JNJ28610244) diminished the tumor growth of human triple negative breast cancer (TNBC) developed in immune-deficient nude mice with MDA-MB-231 cells (Martinel Lamas et al, 2013, 2015b). On the other hand, tumor doubling time was not significantly modified while mean survival was reduced after the treatment with the H4R antagonist JNJ10191584 (Martinel Lamas et al, 2013).…”

Section: H4r Expression In Gynecological and Breast Cancermentioning

confidence: 99%

Pathophysiological Role of Histamine H4 Receptor in Cancer: Therapeutic Implications

2019

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Cancer is a leading cause of death in both developed and developing countries. Although advances in cancer research lead to improved anti-neoplastic therapies, they continue to have unfavorable outcomes, including poor response and severe toxicity. Thus, the challenge for the new therapeutic approaches is to increase anti-tumor efficacy by targeting different molecules encompassed in the tumor and its microenvironment, as well as their specific interactions. The histamine H4 receptor (H4R) is the last discovered histamine receptor subtype and it modulates important immune functions in innate and in adaptive immune responses. Several ligands have been developed and some of them are being used in clinical trials for immune disorders with promising results. When searched in The Cancer Genome Atlas (TCGA) database, human H4R gene was found to be expressed in bladder cancer, kidney cancer, breast cancer, gastrointestinal cancers, lung cancer, endometrial cancer, and skin cancer. In the present work, we aimed to briefly summarize current knowledge in H4R’s pharmacology and in the clinical use of H4R ligands before focusing on recent data reporting the expression of H4R and its pathophysiological role in cancer, representing a potential molecular target for cancer therapeutics. H4R gene and protein expression in different types of cancers compared with normal tissue as well as its relationship with patient prognosis in terms of survival will be described.

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“…Importantly, using different experimental models, in vivo studies showed that histamine is also safe to use as a radioprotective agent of normal radiosensitive tissues, including small intestine, salivary glands and bone marrow (Medina et al ., 2007, 2010, 2011b; Carabajal et al ., 2012). In this regard, it was recently reported that histamine exhibits chemoprotective effects against doxorubicin‐induced cytotoxic and oxidative damage in the heart and liver, without compromising the anti‐tumour activity of doxorubicin (Martinel Lamas et al ., 2015b,2015c).…”

Section: Introductionmentioning

confidence: 99%

Histamine receptors and cancer pharmacology: an update

Massari

Nicoud

Medina

2018

British J Pharmacology

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In the present review, we will discuss the recent advances in the understanding of the role of histamine and histamine receptors in cancer biology. The controversial role of the histaminergic system in different neoplasias including gastric, colorectal, oesophageal, oral, pancreatic, liver, lung, skin, blood and breast cancers will be reviewed. The expression of histamine receptor subtypes, with special emphasis on the histamine H4 receptor, in different cell lines and human tumours, the signal transduction pathways and the associated biological responses as well as the in vivo treatment of experimental tumours with pharmacological ligands will be described. The presented evidence demonstrates that histamine regulates cancer‐associated biological processes during cancer development in multiple cell types, including neoplastic cells and cells in the tumour micro‐environment. The outcome will depend on tumour cell type, the level of expression of histamine receptors, signal transduction associated with these receptors, tumour micro‐environment and histamine metabolism, reinforcing the complexity of cancer disease. Findings show the pivotal role of H4 receptors in the development and progression of many types of cancers, and considering its immunomodulatory properties, the H4 receptor appears to be the most promising molecular therapeutic target for cancer treatment within the histamine receptor family. Furthermore, the H4 receptor is differentially expressed in tumours compared with normal tissues, and in most cancer types in which data are available, H4 receptor expression is associated with clinicopathological characteristics, suggesting that H4 receptors might represent a novel cancer biomarker. Linked Articles This article is part of a themed section on New Uses for 21st Century. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.3/issuetoc

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Histamine: a potential cytoprotective agent to improve cancer therapy?

Cited by 19 publications

References 14 publications

Spatially resolved metabolomics to discover tumor-associated metabolic alterations

Spatially resolved metabolomics to discover tumor-associated metabolic alterations

Pathophysiological Role of Histamine H4 Receptor in Cancer: Therapeutic Implications

Histamine receptors and cancer pharmacology: an update

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