Cimetidine: An anticancer drug?

Kubecová, M; Kološtová, Katarína; Pintérová, Daniela; Kacprzak, Grzegorz; Bobek, Vladimír

doi:10.1016/j.ejps.2011.02.004

Cited by 63 publications

(60 citation statements)

References 79 publications

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“…For instance, glucocorticoids -which are often given to patients with cancer for reducing inflammation-related pain -are potent immunosuppressors 209 . Conversely, histamine blockers -which are normally administered to manage the gastrointestinal side effects of anticancer therapy -reportedly enhance anticancer immune functions 210 .…”

Section: Oncogene Addictionmentioning

confidence: 99%

The secret ally: immunostimulation by anticancer drugs

Galluzzi

Senovilla

Zitvogel

et al. 2012

Nat Rev Drug Discov

607

538

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It has recently become clear that the tumour microenvironment, and in particular the immune system, has a crucial role in modulating tumour progression and response to therapy. Indicators of an ongoing immune response, such as the composition of the intratumoural immune infiltrate, as well as polymorphisms in genes encoding immune modulators, have been correlated with therapeutic outcome. Moreover, several anticancer agents--including classical chemotherapeutics and targeted compounds--stimulate tumour-specific immune responses either by inducing the immunogenic death of tumour cells or by engaging immune effector mechanisms. Here, we discuss the molecular and cellular circuitries whereby cytotoxic agents can activate the immune system against cancer, and their therapeutic implications.

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Section: Oncogene Addictionmentioning

confidence: 99%

The secret ally: immunostimulation by anticancer drugs

Galluzzi

Senovilla

Zitvogel

et al. 2012

Nat Rev Drug Discov

607

538

View full text Add to dashboard Cite

show abstract

“…It has been demonstrated to inhibit tumor growth by several underlying mechanisms, including the inhibition of cancer cell proliferation (20), the blockade of tumor angiogenesis (15) and the enhancement of immune activity (26). A previous study demonstrated that cimetidine induced myeloid-derived suppressor cell apoptosis in mice (27).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, cimetidine inhibited tumor growth in human CCA-bearing mice with no observable adverse effects. As cimetidine is frequently used as H 2 receptor antagonist without serious adverse effects (20,21), it will be useful to repurpose cimetidine for the treatment of CCA.…”

Section: Discussionmentioning

confidence: 99%

Repurposing cimetidine for cholangiocarcinoma: Antitumor effects in vitro and in vivo

et al. 2017

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Abstract. Cimetidine is a histamine type-2 (H 2 ) receptor antagonist that has been demonstrated to have antitumor effects on various types of malignancy. However, its effect on cholangiocarcinoma (CCA), a chemotherapy-resistant bile duct tumor, has yet to be investigated. In the present study, the antitumor activity of cimetidine in vitro and in vivo was evaluated. A methylthiotetrazole assay revealed that the proliferation of certain CCA cell lines was inhibited by cimetidine, which induced the caspase-dependent apoptosis of CCA cells via suppression of the protein kinase B signaling pathway. Suppression of Akt phosphorylation, caspase-3, -8 and -9 activation, phosphotidylserine exposure determined by Annexin V binding assay and the presence of a sub-G1 population were demonstrated by western blotting and flow cytometry analysis. In a CCA xenograft mouse model cimetidine inhibited the growth of CCA cells without observable adverse effects. These results suggest that cimetidine has the potential to be an effective antitumor agent for the treatment of CCA. IntroductionCholangiocarcinoma (CCA) is a highly lethal type of cancer that arises from the bile duct epithelium (1). Although CCA is a rare form of cancer, the global incidence of CCA is increasing, particularly that of the intrahepatic subtype (2). However, the highest incidence of CCA has been reported in the northeast of Thailand where the carcinogenic liver fluke Opisthorchis viverrini is considered a causative agent (3). The early diagnosis of CCA is challenging as patients with CCA typically have non-specific symptoms, and CCA tumor markers are yet to be developed (4). The majority of patients with CCA present with a late-stage disease that is frequently inoperable, and the outcomes of conventional chemotherapy or radiotherapy are unsatisfactory (5). Therefore, a unique approach to developing novel targeting therapies is required to reduce CCA-associated mortality.Cimetidine is an antagonist of histamine type-2 (H 2 ) receptors and is indicated for patients with gastro-esophageal reflux diseases, peptic ulcers or hypersecretory conditions (6,7). The effect of cimetidine on the survival of patients has been reported in various types of cancer, including gastric cancer (8), colorectal cancer (6,9,10), renal cell carcinoma (11), malignant melanoma (12) and glioblastoma (13). Numerous molecular mechanisms underlying the anticancer activities of cimetidine have been revealed, including the inhibition of cell proliferation by blocking the cell growth-promoting effect of histamine (14), the inhibition of tumor angiogenesis (15), the stimulation host immune responses (16) and the suppression of cell adhesion (17). However, the effects of cimetidine in CCA have yet to be demonstrated.In the present study, the anti-CCA activity of cimetidine was examined and the antiproliferative and apoptosis-inducing effects of cimetidine were determined. This was revealed to be partially due to the suppression of protein kinase B (Akt) phosphorylation. A CCA transplant xenogra...

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“…Hence, despite the availability of other alternatives, CIM is considered by the World Health Organization as an essential drug, and still widely used as an anti-ulcer agent. However, in recent years it was demonstrated that CIM has additional pharmacologically useful properties in the areas of modulation of the immune response [17] and odontology [18], as well as in skin [19] and cancer [20][21][22] therapeutics.…”

Section: Introductionmentioning

confidence: 99%