Cimetidine and Other H2 Blockers

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This section does not replicate the other information on this topic but provides additional details or context most relevant to professionals.

Modes of action

Modes of anticancer action of cimetidine are described in several reviews.

• Mechanisms of antitumor action of cimetidine include its ability to interfere with tumor cell adhesion, angiogenesis and proliferation; its effect on the immune system; and inhibition of postoperative immunosuppression.¹Kubecova M, Kolostova K, Pinterova D, Kacprzak G, Bobek V. Cimetidine: an anticancer drug? European Journal of Pharmaceutical Sciences. 2011 Apr 18;42(5):439-44.
• Cimetidine affects the suppressive function of Treg cells by destabilizing their Foxp3 expression.²Zhang Y, Chen Z et al. Cimetidine down-regulates stability of Foxp3 protein via Stub1 in Treg cells. Human Vaccines & Immunotherapeutics. 2016 Oct 2;12(10):2512-2518.
• Clinical and preclinical studies have shown antitumor and anticancer properties of cimetidine. These attributes are mediated by inhibition of tumor cell adhesion, antiangiogenesis and activation of immune system.³Kubecova M, Kolostova K, Pinterova D, Kacprzak G, Bobek V. Cimetidine: an anticancer drug? European Journal of Pharmaceutical Sciences. 2011 Apr18;42(5):439-44.
• Cimetidine, but not ranitidine or famotidine, induced the production of an antitumor cytokine, interleukin (IL)-18, by human monocytes and dendritic cells.⁴Takahashi HK, Watanabe T et al. Cimetidine induces interleukin-18 production through H2-agonist activity in monocytes. Molecular Pharmacology. 2006 Aug;70(2):450-3. 
• There is some evidence for cimetidine’s immunological mechanisms and for effects on E-selectin mediated adhesion.⁵Eaton D, Hawkins RE. Cimetidine in colorectal cancer–are the effects immunological or adhesion-mediated? British Journal of Cancer. 2002;86(2):159–160.

Preclinical evidence

Notable preclinical evidence is presented here; clinical evidence is summarized in How can H2 blockers help you? What the research says ›

Improving treatment outcomes

Anticancer activity in cholangiocarcinoma cells⁶Dana P, Vaeteewoottacharn K et al. Repurposing cimetidine for cholangiocarcinoma: antitumor effects in vitro and in vivo. Oncology Letters. 2017 Mar;13(3):1432-1436.

Anticancer activity in salivary gland cancer cells treated with cimetidine⁷Fukuda M, Tanaka S, Suzuki S, Kusama K, Kaneko T, Sakashita H. Cimetidine induces apoptosis of human salivary gland tumor cells. Oncology Reports. 2007 Mar;17(3):673-8.

Cimetidine enhanced IFN alpha inhibition of clonal growth of leukemic granulocyte-macrophage colony-forming units from chronic myeloid leukemia patients.⁸Douer D, Kneller A et al. Effect of alpha interferon on growth of leukemic and normal hematopoietic progenitors. Synergism with H2 histamine receptor antagonists. Experimental Hematology. 1989 Jun;17(5):443-8.

Managing side effects

Cimetidine protected mice against cisplatin ototoxicity and nephrotoxicity.⁹Ciarimboli G. Membrane transporters as mediators of cisplatin side-effects. Anticancer Research. 2014 Jan;34(1):547-50.

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