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Repeated Administration of Inhibitors for Ion Pumps Reduce Markedly Tumor Growth in Vivo

INTRODUCTION: Measurements of extracellular pH show that the micro environment of malignant tumors is more acidic than that of normal cells, whereas pH does not differ appreciable in normal and malignant cells. The acid micro environment of tumors is created by the secretion of tumor factors and ATP...

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Autores principales: Hrgovic, Igor, Glavic, Zeljko, Kovacic, Zeljko, Mulic, Smaila, Zunic, Lejla, Hrgovic, Zlatko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AVICENA, d.o.o., Sarajevo 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4291850/
https://www.ncbi.nlm.nih.gov/pubmed/24937925
http://dx.doi.org/10.5455/medarh.2014.68.76-78
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author Hrgovic, Igor
Glavic, Zeljko
Kovacic, Zeljko
Mulic, Smaila
Zunic, Lejla
Hrgovic, Zlatko
author_facet Hrgovic, Igor
Glavic, Zeljko
Kovacic, Zeljko
Mulic, Smaila
Zunic, Lejla
Hrgovic, Zlatko
author_sort Hrgovic, Igor
collection PubMed
description INTRODUCTION: Measurements of extracellular pH show that the micro environment of malignant tumors is more acidic than that of normal cells, whereas pH does not differ appreciable in normal and malignant cells. The acid micro environment of tumors is created by the secretion of tumor factors and ATP hydrolysis in hypoxic tumor tissue. In order to survive in a low pH-environment tumor cells develop regulatory mechanisms which keep their intracellular pH stable. Two of the most important systems are the Na+/H+ ion pump and the Na-dependent HCO3-/Cl- pump of stilbenian derivatives. MATERIAL AND METHODS: Experiments were carried out on DBA mice of both sexes at the age of 4 month. Laboratory animals were grown in our institute and supplied with food and aqua ad libitum. RESULTS: After termination of the experiments the mean tumor diameter in the control group was 12.4±0.8mm, in group A it was 6.9±0.6mm, and in group B we measured 6.6±3.1mm. At the final day the tumor size in treated animals was twice as small as in the control group. In addition we observed the rate of survival. In the control group only 18% of the animals were still alive at day 18. Considering the rate of survival a statistically significant difference between treated and untreated animals was observed. The survival of tumor cells is dependent on the function of these ion pumps which keep their intracellular pH values constant in the setting of an acid extracellular environment. CONCLUSION: The activity of the ion pump is especially important at the beginning of cell division and in cell proliferation. Our in vivo experiments demonstrate that prolonged administration of intratumoral ion pump inhibitors suppresses tumor growth as well as enhances survival of tumor-bearing animals. Research of inhibitors of ion pumps and their action in tumor growth opens new perspectives into pathophysiology of malignant tumors and may create new therapeutic options.
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spelling pubmed-42918502015-01-13 Repeated Administration of Inhibitors for Ion Pumps Reduce Markedly Tumor Growth in Vivo Hrgovic, Igor Glavic, Zeljko Kovacic, Zeljko Mulic, Smaila Zunic, Lejla Hrgovic, Zlatko Med Arch Original Paper INTRODUCTION: Measurements of extracellular pH show that the micro environment of malignant tumors is more acidic than that of normal cells, whereas pH does not differ appreciable in normal and malignant cells. The acid micro environment of tumors is created by the secretion of tumor factors and ATP hydrolysis in hypoxic tumor tissue. In order to survive in a low pH-environment tumor cells develop regulatory mechanisms which keep their intracellular pH stable. Two of the most important systems are the Na+/H+ ion pump and the Na-dependent HCO3-/Cl- pump of stilbenian derivatives. MATERIAL AND METHODS: Experiments were carried out on DBA mice of both sexes at the age of 4 month. Laboratory animals were grown in our institute and supplied with food and aqua ad libitum. RESULTS: After termination of the experiments the mean tumor diameter in the control group was 12.4±0.8mm, in group A it was 6.9±0.6mm, and in group B we measured 6.6±3.1mm. At the final day the tumor size in treated animals was twice as small as in the control group. In addition we observed the rate of survival. In the control group only 18% of the animals were still alive at day 18. Considering the rate of survival a statistically significant difference between treated and untreated animals was observed. The survival of tumor cells is dependent on the function of these ion pumps which keep their intracellular pH values constant in the setting of an acid extracellular environment. CONCLUSION: The activity of the ion pump is especially important at the beginning of cell division and in cell proliferation. Our in vivo experiments demonstrate that prolonged administration of intratumoral ion pump inhibitors suppresses tumor growth as well as enhances survival of tumor-bearing animals. Research of inhibitors of ion pumps and their action in tumor growth opens new perspectives into pathophysiology of malignant tumors and may create new therapeutic options. AVICENA, d.o.o., Sarajevo 2014-04-22 2014-04 /pmc/articles/PMC4291850/ /pubmed/24937925 http://dx.doi.org/10.5455/medarh.2014.68.76-78 Text en Copyright: © AVICENA http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Paper
Hrgovic, Igor
Glavic, Zeljko
Kovacic, Zeljko
Mulic, Smaila
Zunic, Lejla
Hrgovic, Zlatko
Repeated Administration of Inhibitors for Ion Pumps Reduce Markedly Tumor Growth in Vivo
title Repeated Administration of Inhibitors for Ion Pumps Reduce Markedly Tumor Growth in Vivo
title_full Repeated Administration of Inhibitors for Ion Pumps Reduce Markedly Tumor Growth in Vivo
title_fullStr Repeated Administration of Inhibitors for Ion Pumps Reduce Markedly Tumor Growth in Vivo
title_full_unstemmed Repeated Administration of Inhibitors for Ion Pumps Reduce Markedly Tumor Growth in Vivo
title_short Repeated Administration of Inhibitors for Ion Pumps Reduce Markedly Tumor Growth in Vivo
title_sort repeated administration of inhibitors for ion pumps reduce markedly tumor growth in vivo
topic Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4291850/
https://www.ncbi.nlm.nih.gov/pubmed/24937925
http://dx.doi.org/10.5455/medarh.2014.68.76-78
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