Histamine and Histamine Receptor Antagonists in Cancer Biology

Abstract

Histamine has been demonstrated to be involved in cell proliferation, embryonic development, and tumour growth. These various biological effects are mediated through the activation of specific histamine receptors (H1, H2, H3, and H4) that differ in their tissue expression patterns and functions. Although many in vitro and in vivo studies of the modulatory roles of histamine in tumour development and metastasis have been reported, the effect of histamine in the progression of some types of tumours remains controversial; however, recent findings on the role of histamine in the immune system have shed new light on this question. This review focuses on the recent advances in understanding the roles of histamine and its receptors in tumour biology. We report our recent observations of the anti-tumoural effect of H1 histamine antagonists on experimental and human melanomas. We have found that in spite of exogenous histamine stimulated human melanoma cell proliferation, clonogenic ability and migration activity in a dose-dependent manner, the melanoma tumour growth was not modulated by in vivo histamine treatment. On the contrary, terfenadine-treatment in vitro induced melanoma cell death by apoptosis and in vivo terfenadine treatment significantly inhibited tumour growth in murine models. These observations increase our understanding of cancer biology and may inspire novel anticancer therapeutic strategies.

Integrative genomic analyses of the histamine H1 receptor and its role in cancer prediction

“…Histamine exerts its functions through binding to G protein-associated histamine H1, H2, H3, and H4 receptors (HRH1, HRH2, HRH3 and HRH4), resulting in the activation of different signal transduction pathways (31)(32)(33). In addition to the human HRH1, in the present study, we identified other HRH1 genes from other 13 vertebrate genomes and found that HRH1 exists in all types of vertebrates including the fish, amphibians, birds and mammals.…”

“…A large number of molecules involved in cell proliferation and key events in tumor development and progression have been extensively investigated including histamine (31)(32)(33). Histamine exerts its functions through binding to G protein-associated histamine H1, H2, H3, and H4 receptors (HRH1, HRH2, HRH3 and HRH4), resulting in the activation of different signal transduction pathways (31)(32)(33).…”

Histamine Receptors as Potential Therapeutic Targets for Cancer Drug Development

“…Additionally, H 2 R antagonists stimulated melanogenesis and inhibited proliferation in B16-C3 mouse melanoma cells (Uçar, 1991). It was also found that melanoma tumour growth was not modulated by in vivo histamine treatment while treatment with terfenadine, an H 1 R antagonist, in vitro induced melanoma cell death by apoptosis and in vivo significantly inhibited tumour growth in murine models (Blaya et al, 2010). Differences between melanoma cells in their capacity to produce and degrade histamine could explain the different sensitivities of melanoma cell types to exogenous histamine treatment.…”

Histamine and Breast Cancer: A New Role for a Well Known Amine

“…Besides this chemotactic action in immune cells it has also been reported that histamine promotes invasiveness specifically through activation of H1 receptor in human cytotrophoblasts required to initiate blastocyst implantation (Liu et al, 2004). Regarding tumor cells it has been reported that histamine acts as a chemoattractant for human carcinoma and melanoma cells via H1 receptor stimulation (Blaya et al, 2010;Tilly et al, 1990). Accordingly, the antiallergic compound tranilast inhibits cell migration and invasion in human malignant glioma cells blocking H1 receptors (Platten et al, 2001).…”

“…It is well known that diverse tumoral tissues and cell lines express the different histamine receptors through which histamine brings about its effects on cell proliferation, differentiation, survival and death. A great deal of evidence shows a relevant role of histamine in tumor progression, however controversial results are published depending on the cell type and the histamine receptor subtype that is activated (Blaya et al, 2010;Francis et al, 2009;Parsons & Ganellin, 2006;Soule et al, 2010). It has also been determined that numerous tumour tissues and cell lines express L-histidine decarboxylase, the histamine-synthesizing enzyme, and contain high levels of endogenous histamine which released to the extracellular media may exert its effects via a paracrine or autocrine regulation Pós et al, 2004;Rivera et al, 2000).…”