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Anti-Cancer Agents in Medicinal Chemistry


ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Review Article

Histamine and Histaminergic Receptors in Colorectal Cancer: From Basic Science to Evidence-based Medicine

Author(s): Giuseppe Losurdo*, Mariabeatrice Principi, Bruna Girardi, Maria Pricci, Michele Barone, Enzo Ierardi and Alfredo Di Leo

Volume 18, Issue 1, 2018

Page: [15 - 20] Pages: 6

DOI: 10.2174/1871520616666160321115349

Price: $65


Background: Histamine is an imidazolic compound performing a crucial function in the pathogenesis of inflammation. Several studies have also emphasized its pro-carcinogenic effect in colorectal cancer (CRC).

Object: In fact, increased histamine levels have been observed in CRC and a decreased catabolism of this molecule is typical of colorectal adenomas. Additional data have demonstrated that CRC is characterized by an altered balance of histamine receptors (HRs); in fact, HR1 and HR4 are down-regulated in CRC, while HR2 is overexpressed.

Method: Based on this evidence, we reviewed several studies investigating the role of HR2 antagonists (HR2A), such as cimetidine in CRC.

Results: From a clinical point of view, HR2A may prolong the survival rates of patients with CRC, and a recent meta-analysis seems to confirm this finding. From a biological perspective, it has been demonstrated that HR2A could have a beneficial effect on CRC for many reasons: i) promotion of peri-tumoral lymphocyte growth and improvement of immune response against the tumor, ii) suppression of adhesion molecules which might favor metastasis, iii) anti-angiogenetic activity (reduction of VEGF), iv) increased production of some cytokines which may counteract tumor growth, such as tumor necrosis factor (TNF) alpha, interleukin (IL)-10 and IL-15. On the contrary, HR1 antagonists did not demonstrate any beneficial effect on CRC. Therefore, it is presumable that histamine could be a relevant player in the development of CRC, but its effect might be mediated by an imperfect homeostasis of its receptors.

Conclusion: In this scenario, HR2A could inhibit carcinogenesis whereas HR2 might act as a pro-carcinogenetic, while HR1 and HR4, being suppressed in CRC, may antagonize neoplastic development.

Keywords: Colorectal cancer, histamine, carcinogenesis, histaminergic receptors, histamine receptor 2 antagonists, receptors.

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