Reduced expression of the retinoblastoma protein shows that the related signaling pathway is essential for mediating the antineoplastic activity of erufosine.

Erufosine is a new antineoplastic agent of the group of alkylphosphocholines, which interferes with signal transduction and induces apoptosis in various leukemic and tumor cell lines. The present study was designed to examine for the first time the mechanism of resistance to erufosine in malignant c...

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Autores principales:	Maya M Zaharieva, Milen Kirilov, Minquang Chai, Stefan M Berger, Spiro Konstantinov, Martin R Berger
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b1d12f7a84f64cbf9ebb18b8f19d9578
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spelling	oai:doaj.org-article:b1d12f7a84f64cbf9ebb18b8f19d95782021-11-25T06:10:00ZReduced expression of the retinoblastoma protein shows that the related signaling pathway is essential for mediating the antineoplastic activity of erufosine.1932-620310.1371/journal.pone.0100950https://doaj.org/article/b1d12f7a84f64cbf9ebb18b8f19d95782014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24987858/?tool=EBIhttps://doaj.org/toc/1932-6203Erufosine is a new antineoplastic agent of the group of alkylphosphocholines, which interferes with signal transduction and induces apoptosis in various leukemic and tumor cell lines. The present study was designed to examine for the first time the mechanism of resistance to erufosine in malignant cells with permanently reduced expression of the retinoblastoma (Rb) protein. Bearing in mind the high number of malignancies with reduced level of this tumor-suppressor, this investigation was deemed important for using erufosine, alone or in combination, in patients with compromised RB1 gene expression. For this purpose, clones of the leukemic T-cell line SKW-3 were used, which had been engineered to constantly express differently low Rb levels. The alkylphosphocholine induced apoptosis, stimulated the expression of the cyclin dependent kinase inhibitor p27Kip1 and inhibited the synthesis of cyclin D3, thereby causing a G2 phase cell cycle arrest and death of cells with wild type Rb expression. In contrast, Rb-deficiency impeded the changes induced by erufosine in the expression of these proteins and abrogated the induction of G2 arrest, which was correlated with reduced antiproliferative and anticlonogenic activities of the compound. In conclusion, analysis of our results showed for the first time that the Rb signaling pathway is essential for mediating the antineoplastic activity of erufosine and its efficacy in patients with malignant diseases may be predicted by determining the Rb status.Maya M ZaharievaMilen KirilovMinquang ChaiStefan M BergerSpiro KonstantinovMartin R BergerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 7, p e100950 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Maya M Zaharieva Milen Kirilov Minquang Chai Stefan M Berger Spiro Konstantinov Martin R Berger Reduced expression of the retinoblastoma protein shows that the related signaling pathway is essential for mediating the antineoplastic activity of erufosine.
description	Erufosine is a new antineoplastic agent of the group of alkylphosphocholines, which interferes with signal transduction and induces apoptosis in various leukemic and tumor cell lines. The present study was designed to examine for the first time the mechanism of resistance to erufosine in malignant cells with permanently reduced expression of the retinoblastoma (Rb) protein. Bearing in mind the high number of malignancies with reduced level of this tumor-suppressor, this investigation was deemed important for using erufosine, alone or in combination, in patients with compromised RB1 gene expression. For this purpose, clones of the leukemic T-cell line SKW-3 were used, which had been engineered to constantly express differently low Rb levels. The alkylphosphocholine induced apoptosis, stimulated the expression of the cyclin dependent kinase inhibitor p27Kip1 and inhibited the synthesis of cyclin D3, thereby causing a G2 phase cell cycle arrest and death of cells with wild type Rb expression. In contrast, Rb-deficiency impeded the changes induced by erufosine in the expression of these proteins and abrogated the induction of G2 arrest, which was correlated with reduced antiproliferative and anticlonogenic activities of the compound. In conclusion, analysis of our results showed for the first time that the Rb signaling pathway is essential for mediating the antineoplastic activity of erufosine and its efficacy in patients with malignant diseases may be predicted by determining the Rb status.
format	article
author	Maya M Zaharieva Milen Kirilov Minquang Chai Stefan M Berger Spiro Konstantinov Martin R Berger
author_facet	Maya M Zaharieva Milen Kirilov Minquang Chai Stefan M Berger Spiro Konstantinov Martin R Berger
author_sort	Maya M Zaharieva
title	Reduced expression of the retinoblastoma protein shows that the related signaling pathway is essential for mediating the antineoplastic activity of erufosine.
title_short	Reduced expression of the retinoblastoma protein shows that the related signaling pathway is essential for mediating the antineoplastic activity of erufosine.
title_full	Reduced expression of the retinoblastoma protein shows that the related signaling pathway is essential for mediating the antineoplastic activity of erufosine.
title_fullStr	Reduced expression of the retinoblastoma protein shows that the related signaling pathway is essential for mediating the antineoplastic activity of erufosine.
title_full_unstemmed	Reduced expression of the retinoblastoma protein shows that the related signaling pathway is essential for mediating the antineoplastic activity of erufosine.
title_sort	reduced expression of the retinoblastoma protein shows that the related signaling pathway is essential for mediating the antineoplastic activity of erufosine.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/b1d12f7a84f64cbf9ebb18b8f19d9578
work_keys_str_mv	AT mayamzaharieva reducedexpressionoftheretinoblastomaproteinshowsthattherelatedsignalingpathwayisessentialformediatingtheantineoplasticactivityoferufosine AT milenkirilov reducedexpressionoftheretinoblastomaproteinshowsthattherelatedsignalingpathwayisessentialformediatingtheantineoplasticactivityoferufosine AT minquangchai reducedexpressionoftheretinoblastomaproteinshowsthattherelatedsignalingpathwayisessentialformediatingtheantineoplasticactivityoferufosine AT stefanmberger reducedexpressionoftheretinoblastomaproteinshowsthattherelatedsignalingpathwayisessentialformediatingtheantineoplasticactivityoferufosine AT spirokonstantinov reducedexpressionoftheretinoblastomaproteinshowsthattherelatedsignalingpathwayisessentialformediatingtheantineoplasticactivityoferufosine AT martinrberger reducedexpressionoftheretinoblastomaproteinshowsthattherelatedsignalingpathwayisessentialformediatingtheantineoplasticactivityoferufosine
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Reduced expression of the retinoblastoma protein shows that the related signaling pathway is essential for mediating the antineoplastic activity of erufosine.

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