DUGi

A nuclear-directed human pancreatic ribonuclease (PE5) targets the metabolic phenotype of cancer cells

http://dugi.udg.edu/item/http:@@@@hdl.handle.net@@2072@@261960

Ribonucleases represent a new class of antitumor RNA-damaging drugs.However, many wild-type members of the vertebrate secreted ribonuclease family arenot cytotoxic because they are not able to evade the cytosolic ribonuclease inhibitor.We previously engineered the human pancreatic ribonuclease to direct it to the cellnucleus where the inhibitor is not present. The best characterized variant is PE5 thatkills cancer cells through apoptosis mediated by the p21WAF1/CIP1 induction and theinactivation of JNK. Here, we have used microarray-derived transcriptional profilingto identify PE5 regulated genes on the NCI/ADR-RES ovarian cancer cell line. RT-qPCRanalyses have confirmed the expression microarray findings. The results show thatPE5 cause pleiotropic effects. Among them, it is remarkable the down-regulation ofmultiple genes that code for enzymes involved in deregulated metabolic pathwaysin cancer cells

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

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