A nuclear-directed human pancreatic ribonuclease (PE5) targets the metabolic phenotype of cancer cells
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Anna Vert1,2, Jessica Castro1,2, Marc Ribó1,2, Antoni Benito1,2, Maria Vilanova1,2
1Laboratori d'Enginyeria de Proteïnes, Departament de Biologia, Facultat de Ciències, Universitat de Girona, Girona, Spain
2Institut d’Investigació Biomèdica de Girona Josep Trueta, (IdIBGi), Girona, Spain
Maria Vilanova, email: email@example.com
Antoni Benito, email: firstname.lastname@example.org
Keywords: antitumor drug, human pancreatic ribonuclease, metabolism of cancer cells, microarray profiling, tumor cell death
Received: December 18, 2015 Accepted: February 11, 2016 Published: February 22, 2016
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.
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