Use of Proton Pump Inhibitors as Adjunct Treatment for Triple-Negative Breast Cancers. An Introductory Study

Goh, Wayne; Sleptsova-Freidrich, Inna; Petrović, Nenad

doi:10.18433/j34608

Cited by 46 publications

(52 citation statements)

References 24 publications

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“…Omeprazole is a proton pump inhibitor that is capable of inhibiting acid secretion without binding H2 receptors. Other studies have shown that omeprazole can inhibit breast cancer cell proliferation in vitro and experimental metastasis in vivo , 57,58 but our results show that, unlike ranitidine, omeprazole treatment does not inhibit E0771 tumor growth.…”

Section: Discussioncontrasting

confidence: 90%

Ranitidine modifies myeloid cell populations and inhibits breast tumor development and spread in mice

et al. 2016

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Histamine receptor 2 (H2) antagonists are widely used clinically for the control of gastrointestinal symptoms, but also impact immune function. They have been reported to reduce tumor growth in established colon and lung cancer models. Histamine has also been reported to modify populations of myeloid-derived suppressor cells (MDSCs). We have examined the impact of the widely used H2 antagonist ranitidine, on both myeloid cell populations and tumor development and spread, in three distinct models of breast cancer that highlight different stages of cancer progression. Oral ranitidine treatment significantly decreased the monocytic MDSC population in the spleen and bone marrow both alone and in the context of an orthotopic breast tumor model. H2 antagonists ranitidine and famotidine, but not H1 or H4 antagonists, significantly inhibited lung metastasis in the 4T1 model. In the E0771 model, ranitidine decreased primary tumor growth while omeprazole treatment had no impact on tumor development. Gemcitabine treatment prevented the tumor growth inhibition associated with ranitidine treatment. In keeping with ranitidine-induced changes in myeloid cell populations in non-tumor-bearing mice, ranitidine also delayed the onset of spontaneous tumor development, and decreased the number of tumors that developed in LKB1−/−/NIC mice. These results indicate that ranitidine alters monocyte populations associated with MDSC activity, and subsequently impacts breast tumor development and outcome. Ranitidine has potential as an adjuvant therapy or preventative agent in breast cancer and provides a novel and safe approach to the long-term reduction of tumor-associated immune suppression.

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Section: Discussioncontrasting

confidence: 90%

Ranitidine modifies myeloid cell populations and inhibits breast tumor development and spread in mice

et al. 2016

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“…Subsequent work showed that the pH i -dependent proliferative response in cancer cells can be generated by distinct ion transport proteins, including NHE1 (Lauritzen et al, 2012), Na + -driven bicarbonate transporters (Boedtkjer et al, 2013;McIntyre et al, 2016) and the H + /K + -ATPase proton pump (Goh et al, 2014). Additionally, pH i -dependent proliferation has recently been confirmed in vivo (Grillo-Hill et al, 2015).…”

Section: Proliferation and Cell Survivalmentioning

confidence: 99%

Cancer cell behaviors mediated by dysregulated pH dynamics at a glance

White

Grillo-Hill

Barber

2017

Journal of Cell Science

297

312

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Dysregulated pH is a common characteristic of cancer cells, as they have an increased intracellular pH ( pH i ) and a decreased extracellular pH ( pH e ) compared with normal cells. Recent work has expanded our knowledge of how dysregulated pH dynamics influences cancer cell behaviors, including proliferation, metastasis, metabolic adaptation and tumorigenesis. Emerging data suggest that the dysregulated pH of cancers enables these specific cell behaviors by altering the structure and function of selective pH-sensitive proteins, termed pH sensors. Recent findings also show that, by blocking pH i increases, cancer cell behaviors can be attenuated. This suggests ion transporter inhibition as an effective therapeutic approach, either singly or in combination with targeted therapies. In this Cell Science at a Glance article and accompanying poster, we highlight the interconnected roles of dysregulated pH dynamics in cancer initiation, progression and adaptation.

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“…Omeprazole reportedly prevented azoxymethane-induced colonic aberrant crypt foci development in male F344 rats as well as reducing HCT-116 and HCA-7 colon cancer cell growth [230]. Esomeprazole was found to inhibit MDA-MB 468 triple negative breast cancer cell growth while rabeprazole had growth inhibitory effects on MKN 28 and AGS gastric cancer cell lines [231,232]. In addition, lansoprazole has been investigated for its ability to stimulate MDA-MB-231 breast cancer cell death in a dose dependent manner [233].…”

Section: Implications For Cancer Therapy and Chemopreventionmentioning

confidence: 99%

Molecular Connections between Cancer Cell Metabolism and the Tumor Microenvironment

Justus

Sanderlin

Yang

2015

IJMS

126

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Cancer cells preferentially utilize glycolysis, instead of oxidative phosphorylation, for metabolism even in the presence of oxygen. This phenomenon of aerobic glycolysis, referred to as the “Warburg effect”, commonly exists in a variety of tumors. Recent studies further demonstrate that both genetic factors such as oncogenes and tumor suppressors and microenvironmental factors such as spatial hypoxia and acidosis can regulate the glycolytic metabolism of cancer cells. Reciprocally, altered cancer cell metabolism can modulate the tumor microenvironment which plays important roles in cancer cell somatic evolution, metastasis, and therapeutic response. In this article, we review the progression of current understandings on the molecular interaction between cancer cell metabolism and the tumor microenvironment. In addition, we discuss the implications of these interactions in cancer therapy and chemoprevention.

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Use of Proton Pump Inhibitors as Adjunct Treatment for Triple-Negative Breast Cancers. An Introductory Study

Cited by 46 publications

References 24 publications

Ranitidine modifies myeloid cell populations and inhibits breast tumor development and spread in mice

Ranitidine modifies myeloid cell populations and inhibits breast tumor development and spread in mice

Cancer cell behaviors mediated by dysregulated pH dynamics at a glance

Molecular Connections between Cancer Cell Metabolism and the Tumor Microenvironment

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