title: A nuclear-directed human pancreatic ribonuclease (PE5) targets the metabolic phenotype of cancer cells.
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 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.
authors.affiliation: Laboratori d'Enginyeria de Proteïnes, Departament de Biologia, Facultat de Ciències, Universitat de Girona, Girona, Spain.|Institut d'Investigació Biomèdica de Girona Josep Trueta, (IdIBGi), Girona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Vert
authors.affiliation: Laboratori d'Enginyeria de Proteïnes, Departament de Biologia, Facultat de Ciències, Universitat de Girona, Girona, Spain.|Institut d'Investigació Biomèdica de Girona Josep Trueta, (IdIBGi), Girona, Spain.
authors.forename: Jessica
authors.initials: J
authors.lastname: Castro
authors.affiliation: Laboratori d'Enginyeria de Proteïnes, Departament de Biologia, Facultat de Ciències, Universitat de Girona, Girona, Spain.|Institut d'Investigació Biomèdica de Girona Josep Trueta, (IdIBGi), Girona, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Ribó
authors.affiliation: Laboratori d'Enginyeria de Proteïnes, Departament de Biologia, Facultat de Ciències, Universitat de Girona, Girona, Spain.|Institut d'Investigació Biomèdica de Girona Josep Trueta, (IdIBGi), Girona, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Benito
authors.affiliation: Laboratori d'Enginyeria de Proteïnes, Departament de Biologia, Facultat de Ciències, Universitat de Girona, Girona, Spain.|Institut d'Investigació Biomèdica de Girona Josep Trueta, (IdIBGi), Girona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Vilanova
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D053858:Metabolic Networks and Pathways / Q000187:drug effects / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D010926:Placental Hormones / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012259:Ribonuclease, Pancreatic / Q000378:metabolism / Q000494:pharmacology*; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D010926:Placental Hormones; D017382:Reactive Oxygen Species; D025521:Tumor Suppressor Proteins; C022052:placental ribonuclease inhibitor; D048031:JNK Mitogen-Activated Protein Kinases; D012259:Ribonuclease, Pancreatic; D005947:Glucose
keywords: antitumor drug; human pancreatic ribonuclease; metabolism of cancer cells; microarray profiling; tumor cell death