http://www.cnr.it/ontology/cnr/individuo/prodotto/ID27701

Erucylphosphohomocholine, the first intravenously applicable alkylphosphocholine, is cytotoxic to acute myelogenous leukemia cells through JNK- and PP2A-dependent mechanisms. (Articolo in rivista)

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Erucylphosphohomocholine, the first intravenously applicable alkylphosphocholine, is cytotoxic to acute myelogenous leukemia cells through JNK- and PP2A-dependent mechanisms. (Articolo in rivista) (literal)

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Martelli AM, Papa V, Tazzari PL, Ricci F, Evangelisti C, Chiarini F, Grimaldi C, Cappellini A, Martinelli G, Ottaviani E, Pagliaro P, Horn S, Bäsecke J, Lindner LH, Eibl H, McCubrey JA. (2010)
Erucylphosphohomocholine, the first intravenously applicable alkylphosphocholine, is cytotoxic to acute myelogenous leukemia cells through JNK- and PP2A-dependent mechanisms.
in Leukemia
(literal)

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Martelli AM, Papa V, Tazzari PL, Ricci F, Evangelisti C, Chiarini F, Grimaldi C, Cappellini A, Martinelli G, Ottaviani E, Pagliaro P, Horn S, Bäsecke J, Lindner LH, Eibl H, McCubrey JA. (literal)

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Department of Human Anatomical Sciences, University of Bologna, Bologna, Italy; IGM-CNR, c/o IOR, Bologna, Italy; Department of Health Sciences, University of Cassino, Cassino, Italy; Transfusion Center, Policlinico S. Orsola-Malpighi, Bologna, Italy; Department of Hematology/Oncology, University of Bologna, Bologna, Italy; Interdisziplina¨re Klinik und Poliklinik fu¨ r Stammzelltransplantation, Forschungsabteilung Zell- und Gentherapie, University of Hamburg, Hamburg, Germany; Division of Hematology and Oncology, Department of Medicine, University of Goettingen, Goettingen, Germany; Department of Internal Medicine III, Hospital of the University of Munich, Munich, Germany; Max Planck Institute for Biophysical Chemistry, Goettingen, Germany; Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC, USA (literal)

Titolo

Erucylphosphohomocholine, the first intravenously applicable alkylphosphocholine, is cytotoxic to acute myelogenous leukemia cells through JNK- and PP2A-dependent mechanisms. (literal)

Abstract

Alkylphospholipids and alkylphosphocholines (APCs) are promising antitumor agents, which target the plasma membrane and affect multiple signal transduction networks. We investigated the therapeutic potential of erucylphosphohomocholine (ErPC3), the first intravenously applicable APC, in human acute myelogenous leukemia (AML) cells. ErPC3 was tested on AML cell lines, as well as AML primary cells. At short (6-12 h) incubation times, the drug blocked cells in G2/M phase of the cell cycle, whereas, at longer incubation times, it decreased survival and induced cell death by apoptosis. ErPC3 caused JNK 1/2 activation as well as ERK 1/2 dephosphorylation. Pharmacological inhibition of caspase-3 or a JNK 1/2 inhibitor peptide markedly reduced ErPC3 cytotoxicity. Protein phosphatase 2A downregulation by siRNA opposed ERK 1/2 dephosphorylation and blunted the cytotoxic effect of ErPC3. ErPC3 was cytotoxic to AML primary cells and reduced the clonogenic activity of CD34(+) leukemic cells. ErPC3 induced a significant apoptosis in the compartment (CD34(+) CD38(Low/Neg) CD123(+)) enriched in putative leukemia-initiating cells. This conclusion was supported by ErPC3 cytotoxicity on AML blasts showing high aldehyde dehydrogenase activity and on the side population of AML cell lines and blasts. These findings indicate that ErPC3 might be a promising therapeutic agent for the treatment of AML patients. (literal)

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