RRC ID 61237
Author Nakajima Y, Kanno T, Nagaya T, Kuribayashi K, Nakano T, Gotoh A, Nishizaki T.
Title Adenosine deaminase inhibitor EHNA exhibits a potent anticancer effect against malignant pleural mesothelioma.
Journal Cell Physiol Biochem
Abstract BACKGROUND/AIMS:Malignant pleural mesothelioma (MPM) is an aggressive malignant tumor and an effective therapy has been little provided as yet. The present study investigated the possibility for the adenosine deaminase (ADA) inhibitor EHNA as a target of MPM treatment.
METHODS:MTT assay, TUNEL staining, monitoring of intracellular adenosine concentrations, and Western blotting were carried out in cultured human MPM cell lines without and with knocking-down ADA. The in vivo effect of EHNA was assessed in mice inoculated with NCI-H2052 MPM cells.
RESULTS:EHNA induced apoptosis of human MPM cell lines in a concentration (0.01-1 mM)- and treatment time (24-48 h)-dependent manner, but such effect was not obtained with another ADA inhibitor pentostatin. EHNA increased intracellular adenosine concentrations in a treatment time (3-9 h)-dependent manner. EHNA-induced apoptosis of MPM cells was mimicked by knocking-down ADA, and the effect was neutralized by the adenosine kinase inhibitor ABT-702. EHNA clearly suppressed tumor growth in mice inoculated with NCI-H2052 MPM cells.
CONCLUSION:The results of the present study show that EHNA induces apoptosis of MPM cells by increasing intracellular adenosine concentrations, to convert to AMP, and effectively prevents MPM cell proliferation. This suggests that EHNA may be useful for treatment of the tragic neoplasm MPM.
Volume 35(1)
Pages 51-60
Published 2015-1-1
DOI 10.1159/000369674
PII 000369674
PMID 25547995
MeSH Adenine / analogs & derivatives* Adenine / therapeutic use Adenine / toxicity Adenosine / metabolism Adenosine Deaminase / chemistry Adenosine Deaminase / genetics Adenosine Deaminase / metabolism* Adenosine Deaminase Inhibitors / therapeutic use Adenosine Deaminase Inhibitors / toxicity* Animals Apoptosis / drug effects Cell Line, Tumor Cell Proliferation / drug effects Humans Mesothelioma / drug therapy Mesothelioma / pathology Mice Mice, Nude Morpholines / pharmacology Pleural Neoplasms / drug therapy Pleural Neoplasms / pathology Pyrimidines / pharmacology RNA Interference RNA, Small Interfering / metabolism Transplantation, Heterologous
IF 5.5
Human and Animal Cells HeLa(RCB0007) Hep G2(RCB1648)