Characterization of the Gastroprotective Effects of N, N-diethyl-2-[4-(phenylmethyl)phenoxy]-ethanamine Hydrochloride, a Non-H&lt;sub&gt;1&lt;/sub&gt;/Non- H&lt;sub&gt;2&lt;/sub&gt; Histamine Antagonist

Glavin, Gary B.; Gerrard, Jon M.

doi:10.1159/000200489

Cited by 9 publications

(3 citation statements)

References 17 publications

(25 reference statements)

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“…28 In addition to its protection of the bone marrow, a cytoprotective effect of DPPE in the gut of rats exposed to cold-restraint stress has been linked to the induction of a 10-fold increase in levels of prostacyclin (PGI 2 ). 32…”

Section: L-histidinol and Dppe: Dissimilar Agents With Similar Effects On Histamine Binding Dna Synthesis Cytoprotection And Chemopotentimentioning

confidence: 99%

“…The observation that DPPE causes (1) lowconcentration stimulation and high-concentration inhibition of DNA synthesis in MCF-7 breast cancer cells in vitro; (2) stimulation of inflammation and mitotic activity in phorbol-painted skin 29 ; (3) growth-stimulation of rodent tumors; and (4) induction of high levels of PGI 2 in the gut, 32 raises the possibility that, like its cytoprotective effects, chemopotentiation by DPPE may be linked to its interaction with P450s and/or lipoxygenases involved in arachidonate metabolism. An interaction with these enzymes might result in an increase or decrease in cellular levels of various lipids and eicosanoids that, depending on their concentration, stimulate or inhibit DNA synthesis.…”

Section: Hormetic Effect On Dna Synthesis and Chemopotentiation By Dppe May Be Linked To The Modulation Of Arachidonate Metabolismmentioning

confidence: 99%

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N,N-diethyl-2-[4-(phenylmethyl) phenoxy] ethanamine (DPPE; tesmilifene), a chemopotentiating agent with hormetic effects on DNA synthesis in vitro, may improve survival in patients with metastatic breast cancer

Brandes

2008

Hum Exp Toxicol

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N,N-diethyl-2-[4-(phenylmethyl) phenoxy] ethanamine (DPPE; tesmilifene) is a novel anti-histaminic and chemopotentiating agent that has a hormetic effect on DNA synthesis in MCF (Michigan Cancer Foundation)-7 human breast cancer cells in vitro and stimulates the growth of experimental tumors in rodents. In a prospectively randomized phase three trial (NCIC MA.19), 152 patients who were co-administered DPPE and doxorubicin survived 50% longer ( P < 0.03) than 153 patients who were administered the same dose and schedule of doxorubicin alone. At clinically relevant in vitro concentrations that do not inhibit the P-glycoprotein (P-gp) pump, DPPE selectively sensitizes the cancer cells that express the multiple drug resistance phenotype, making them more susceptible to the cytotoxic effects of chemotherapeutic agents, including anthracyclines and taxanes. Based on its previously demonstrated interaction with histamine at CYP3A4, a P450 that metabolizes arachidonic acid, and its induction of high levels of prostacyclin in the gut of rodents, modulation by DPPE of the intracellular concentration of arachidonate products, such as hydroxyeicosatetraeinoic acids, implicated in increased cancer cell proliferation and metastasis, is postulated.

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Section: L-histidinol and Dppe: Dissimilar Agents With Similar Effects On Histamine Binding Dna Synthesis Cytoprotection And Chemopotentimentioning

confidence: 99%

Section: Hormetic Effect On Dna Synthesis and Chemopotentiation By Dppe May Be Linked To The Modulation Of Arachidonate Metabolismmentioning

confidence: 99%

N,N-diethyl-2-[4-(phenylmethyl) phenoxy] ethanamine (DPPE; tesmilifene), a chemopotentiating agent with hormetic effects on DNA synthesis in vitro, may improve survival in patients with metastatic breast cancer

Brandes

2008

Hum Exp Toxicol

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“…For the immunohistochemical detection of HDC in bone marrow colonies of progenitor cells, a primary antibody was raised in chickens against the 318-325 (VKD-KYKLQ) residues of the full HDC protein [9]. FITC-labelled anti-chicken antibody was used for localization of the enzyme protein.…”

Section: Morphological Demonstration Of Histidine Decarboxylase (Hdc)mentioning

confidence: 99%

Murine and human hematopoietic colony formation: a possible regulatory role for intracellular histamine

Bencsáth

Gidáli

Brandes

et al. 2002

Acta Biologica Hungarica

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Increasing number of data suggests that locally produced histamine is involved in regulation of hematopoiesis. In this study the granulocyte/macrophage (CFU-GM) colony formation by normal murine or human bone marrow cells, leukaemic colony formation (CFU-L) by a murine leukemia cell line (WEHI 3B), and colony formation by bone marrow cells from patients with chronic myeloid leukemia (CML) have been examined. We detected mRNA and protein expression of histidine decarboxylase (HDC), the only enzyme responsible for histamine synthesis both in normal bone marrow progenitor cells and in leukaemic progenitors. The significance of in situ generated histamine was shown on colony formation by inhibitory action of alphaFMH (blocking HDC activity, i.e. de novo histamine formation) and by N,N-diethyl-2-[4-(phenylmethyl)phenoxy]-ethanamine-HCl (DPPE) disturbing the interference of histamine with intracellular binding sites. These data provide further confirmation of the role of histamine in development and colony formation of bone marrow derived cells.

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Histidine decarboxylase in peripheral lymphocytes of healthy individuals and chronic lymphoid leukemia patients

Bencsáth

Pálóczi

Szalai

et al. 1998

Pathol. Oncol. Res.

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Histidine decarboxylase (HDC), the only enzyme capable of synthetizing histamine, has been found in many proliferating cells and tissues suggesting a role of histamine in cellular proliferation. In this study expression of HDC and the significance of histamine in the proliferation of peripheral lymphocytes of five healthy persons and six patients with chronic lymphoid leukemia (CLL) was examined. Expression of HDC mRNA and the protein was proved by reverse transcriptase polymerase chain reaction and by immunoblot, respectively. The role of histamine was studied in proliferation assays in the presence of irreversible inhibitor of the HDC (alpha-fluoromethylhistidine--aFMH) and also by competing for the intracellular binding sites of histamine using N,N-diethyl-2, 4-phenylmethyl-phenoxy-ethanamine-HCl (DPPE). By inhibiting the HDC enzyme activity by FMH and blocking the intracellular action of histamine by DPPE, a significant decrease in cell proliferation was observed in mitogen stimulated lymphocytes of healthy donors. In CLL patients the proliferation of leukemic lymphocytes was significantly inhibited by blocking the binding of histamine to intracellular binding sites by DPPE but not by FMH inhibiting only the de novo histamine formation. The observations suggest that HDC has functional relevance in lymphocytes, since mitogen induced lymphocyte proliferation of healthy donors is mainly enhanced by de novo synthesis and subsequent action of intracellular histamine. Alternatively, in constitutively proliferating chronic lymphoid leukemia cells we suggest that the preformed pool but not the de novo synthesized intracellular histamine interferes with cellular proliferation.

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Characterization of the Gastroprotective Effects of N, N-diethyl-2-[4-(phenylmethyl)phenoxy]-ethanamine Hydrochloride, a Non-H<sub>1</sub>/Non- H<sub>2</sub> Histamine Antagonist

Cited by 9 publications

References 17 publications

N,N-diethyl-2-[4-(phenylmethyl) phenoxy] ethanamine (DPPE; tesmilifene), a chemopotentiating agent with hormetic effects on DNA synthesis in vitro, may improve survival in patients with metastatic breast cancer

N,N-diethyl-2-[4-(phenylmethyl) phenoxy] ethanamine (DPPE; tesmilifene), a chemopotentiating agent with hormetic effects on DNA synthesis in vitro, may improve survival in patients with metastatic breast cancer

Murine and human hematopoietic colony formation: a possible regulatory role for intracellular histamine

Histidine decarboxylase in peripheral lymphocytes of healthy individuals and chronic lymphoid leukemia patients

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