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...

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Bibliographic Details
Published in:Oncotarget 2016-04, Vol.7 (14), p.18309-18324
Main Authors: Vert, Anna, Castro, Jessica, Ribó, Marc, Benito, Antoni, Vilanova, Maria
Format: Article
Language:English
Subjects:
Antineoplastic Agents - pharmacology
Apoptosis - drug effects
Cancer
Cancer cells
Cell Line, Tumor
Cell Proliferation - drug effects
Cyclin-Dependent Kinase Inhibitor p21 - metabolism
Càncer
Cèl·lules canceroses
Down-Regulation - drug effects
Female
Glucose - metabolism
Humans
JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors
Metabolic Networks and Pathways - drug effects
Metabolic Networks and Pathways - genetics
Ovarian Neoplasms - drug therapy
Ovarian Neoplasms - metabolism
Ovarian Neoplasms - pathology
Placental Hormones - metabolism
Reactive Oxygen Species - metabolism
Research Paper
Ribonuclease, Pancreatic - metabolism
Ribonuclease, Pancreatic - pharmacology
Ribonucleases
Tractament
Treatment
Tumor Suppressor Proteins - biosynthesis
Tumor Suppressor Proteins - genetics
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Summary: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.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.7579