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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 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 p21WAF1/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

This work has been supported by grants BFU2009-06935 and BIO2013-43517 from MINECO (Spain) and SING12/0 from UdG (Spain).

Impact Journals

Manager: Ministerio de Ciencia e Innovación (Espanya)
Ministerio de Economía y Competitividad (Espanya)
Author: Vert Company, Anna
Castro Gallegos, Jessica
Ribó i Panosa, Marc
Benito i Mundet, Antoni
Vilanova i Brugués, Maria
Date: 2016
Abstract: 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 p21WAF1/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
This work has been supported by grants BFU2009-06935 and BIO2013-43517 from MINECO (Spain) and SING12/0 from UdG (Spain).
Format: application/pdf
Document access: http://hdl.handle.net/10256/12447
Language: eng
Publisher: Impact Journals
Collection: info:eu-repo/semantics/altIdentifier/doi/10.18632/oncotarget.7579
info:eu-repo/semantics/altIdentifier/issn/1949-2553
info:eu-repo/grantAgreement/MICINN//BFU2009-06935/ES/Bases Moleculares Del Plegamiento Y Citotoxicidad De Las Ribonucleasas Pancreaticas. Evaluacion De La Actividad Citotoxica Y Diseño De Estrategias Para Su Control Mediante Splicing Proteico./
info:eu-repo/grantAgreement/MINECO//BIO2013-43517-R/ES/RIBONUCLEASAS E INTEINAS COMO HERRAMIENTAS MOLECULARES PARA EL DESARROLLO DE FARMACOS ANTITUMORALES Y ESTUDIO DE PROTEINOPATIAS/
Rights: Attribution 3.0 Spain
Rights URI: http://creativecommons.org/licenses/by/3.0/es/
Subject: Càncer -- Tractament
Cancer -- Treatment
Ribonucleases
Cèl·lules canceroses
Cancer cells
Title: A nuclear-directed human pancreatic ribonuclease (PE5) targets the metabolic phenotype of cancer cells
Type: info:eu-repo/semantics/article
Repository: DUGiDocs

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