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A nuclear-directed human pancreatic ribonuclease (PE5) targets the metabolic phenotype of cancer cells
Ribonucleases represent a new class of antitumor RNA-damaging drugs. However, many wild-type members of the vertebrate secreted ribonuclease family are not cytotoxic because they are not able to evade the cytosolic ribonuclease inhibitor. We previously engineered the human pancreatic ribonuclease to...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4951290/ https://www.ncbi.nlm.nih.gov/pubmed/26918450 http://dx.doi.org/10.18632/oncotarget.7579 |
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author | Vert, Anna Castro, Jessica Ribó, Marc Benito, Antoni Vilanova, Maria |
author_facet | Vert, Anna Castro, Jessica Ribó, Marc Benito, Antoni Vilanova, Maria |
author_sort | Vert, Anna |
collection | PubMed |
description | Ribonucleases represent a new class of antitumor RNA-damaging drugs. However, many wild-type members of the vertebrate secreted ribonuclease family are not cytotoxic because they are not able to evade the cytosolic ribonuclease inhibitor. We previously engineered the human pancreatic ribonuclease to direct it to the cell nucleus where the inhibitor is not present. The best characterized variant is PE5 that kills cancer cells through apoptosis mediated by the p21(WAF1/CIP1) induction and the inactivation of JNK. Here, we have used microarray-derived transcriptional profiling to identify PE5 regulated genes on the NCI/ADR-RES ovarian cancer cell line. RT-qPCR analyses have confirmed the expression microarray findings. The results show that PE5 cause pleiotropic effects. Among them, it is remarkable the down-regulation of multiple genes that code for enzymes involved in deregulated metabolic pathways in cancer cells. |
format | Online Article Text |
id | pubmed-4951290 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-49512902016-07-21 A nuclear-directed human pancreatic ribonuclease (PE5) targets the metabolic phenotype of cancer cells Vert, Anna Castro, Jessica Ribó, Marc Benito, Antoni Vilanova, Maria Oncotarget Research Paper Ribonucleases represent a new class of antitumor RNA-damaging drugs. However, many wild-type members of the vertebrate secreted ribonuclease family are not cytotoxic because they are not able to evade the cytosolic ribonuclease inhibitor. We previously engineered the human pancreatic ribonuclease to direct it to the cell nucleus where the inhibitor is not present. The best characterized variant is PE5 that kills cancer cells through apoptosis mediated by the p21(WAF1/CIP1) induction and the inactivation of JNK. Here, we have used microarray-derived transcriptional profiling to identify PE5 regulated genes on the NCI/ADR-RES ovarian cancer cell line. RT-qPCR analyses have confirmed the expression microarray findings. The results show that PE5 cause pleiotropic effects. Among them, it is remarkable the down-regulation of multiple genes that code for enzymes involved in deregulated metabolic pathways in cancer cells. Impact Journals LLC 2016-02-22 /pmc/articles/PMC4951290/ /pubmed/26918450 http://dx.doi.org/10.18632/oncotarget.7579 Text en Copyright: © 2016 Vert et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Vert, Anna Castro, Jessica Ribó, Marc Benito, Antoni Vilanova, Maria A nuclear-directed human pancreatic ribonuclease (PE5) targets the metabolic phenotype of cancer cells |
title | A nuclear-directed human pancreatic ribonuclease (PE5) targets the metabolic phenotype of cancer cells |
title_full | A nuclear-directed human pancreatic ribonuclease (PE5) targets the metabolic phenotype of cancer cells |
title_fullStr | A nuclear-directed human pancreatic ribonuclease (PE5) targets the metabolic phenotype of cancer cells |
title_full_unstemmed | A nuclear-directed human pancreatic ribonuclease (PE5) targets the metabolic phenotype of cancer cells |
title_short | A nuclear-directed human pancreatic ribonuclease (PE5) targets the metabolic phenotype of cancer cells |
title_sort | nuclear-directed human pancreatic ribonuclease (pe5) targets the metabolic phenotype of cancer cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4951290/ https://www.ncbi.nlm.nih.gov/pubmed/26918450 http://dx.doi.org/10.18632/oncotarget.7579 |
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