Histamine receptors and cancer pharmacology: an update

Abstract

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

Circulating basophil count as a prognostic marker of tumor aggressiveness and survival outcomes in colorectal cancer

“…The four histamine receptor subtypes are widely distributed throughout the digestive system and all histamine receptor subtypes are involved in cancer, including CRC. Histamine could suppress colorectal tumorigenesis and severity of inflammation‐associated colon cancer in HDC KO mice [25,26]. Yet a low expression level of histamine receptors and histamine receptor gene was demonstrated in colon adenocarcinoma compared with normal colonic tissue [27].…”

Development of a Rapid and Eco-Friendly UHPLC Analytical Method for the Detection of Histamine in Fish Products

“…Furthermore, several factors, such as transport and storage conditions, could lead to the formation of a food contaminant called histamine [ 8 , 9 ]. Histamine (2-(4-imidazolyl) ethylamine) is a biogenic amine that plays an important role in the inflammatory and allergic responses of humans [ 10 ]. Histamine is produced by proteolytic bacteria from the decarboxylation of the amino acid histidine [ 6 , 11 ].…”

The antihistamine deptropine induces hepatoma cell death through blocking autophagosome-lysosome fusion

“…HRs are expressed in several human normal and tumor cells and tissues; for example, hepatocytes express the H1, H2, and H3 HRs [33]. All four types of HRs may be expressed in human and mouse hepatoma cells, and the H4 HR is increased in human HCC primary tumors compared to normal liver tissues [34].…”