Affiliation:
1. Gastroenterology Division, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
Abstract
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.
Publisher
Bentham Science Publishers Ltd.
Subject
Cancer Research,Pharmacology,Molecular Medicine
Cited by
13 articles.
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