Inhibition of glucose-6-phosphate dehydrogenase sensitizes cisplatin-resistant cells to death

The mechanisms of cisplatin resistance, one of the major limitations of current chemotherapy, has only partially been described. We previously demonstrated that cisplatin-resistant ovarian cancer cells (C13), are characterized by reduced mitochondrial activity and higher glucose-dependency when comp...

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Main Authors:	Catanzaro, Daniela, Gaude, Edoardo, Orso, Genny, Giordano, Carla, Guzzo, Giulia, Rasola, Andrea, Ragazzi, Eugenio, Caparrotta, Laura, Frezza, Christian, Montopoli, Monica
Format:	Online
Language:	English
Published:	Impact Journals LLC 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4745784/

id	pubmed-4745784
recordtype	oai_dc
spelling	pubmed-47457842016-02-23 Inhibition of glucose-6-phosphate dehydrogenase sensitizes cisplatin-resistant cells to death Catanzaro, Daniela Gaude, Edoardo Orso, Genny Giordano, Carla Guzzo, Giulia Rasola, Andrea Ragazzi, Eugenio Caparrotta, Laura Frezza, Christian Montopoli, Monica Research Paper The mechanisms of cisplatin resistance, one of the major limitations of current chemotherapy, has only partially been described. We previously demonstrated that cisplatin-resistant ovarian cancer cells (C13), are characterized by reduced mitochondrial activity and higher glucose-dependency when compared to the cisplatin-sensitive counterpart (2008). In this work we further characterized the role of metabolic transformation in cisplatin resistance. By using transmitochondrial hybrids we show that metabolic reprogramming of cisplatin-resistant cell is not caused by inherent mtDNA mutations. We also found that C13 cells not only present an increased glucose-uptake and consumption, but also exhibit increased expression and enzymatic activity of the Pentose Phosphate pathway (PPP) enzyme Glucose-6-Phosphate Dehydrogenase (G6PDH). Moreover, we show that cisplatin-resistant cells are more sensitive to G6PDH inhibition. Even if the metabolomic fingerprint of ovarian cancer cells remains to be further elucidated, these findings indicate that PPP offers innovative potential targets to overcome cisplatin resistance. Impact Journals LLC 2015-08-17 /pmc/articles/PMC4745784/ /pubmed/26337086 Text en Copyright: © 2015 Catanzaro et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Catanzaro, Daniela Gaude, Edoardo Orso, Genny Giordano, Carla Guzzo, Giulia Rasola, Andrea Ragazzi, Eugenio Caparrotta, Laura Frezza, Christian Montopoli, Monica
spellingShingle	Catanzaro, Daniela Gaude, Edoardo Orso, Genny Giordano, Carla Guzzo, Giulia Rasola, Andrea Ragazzi, Eugenio Caparrotta, Laura Frezza, Christian Montopoli, Monica Inhibition of glucose-6-phosphate dehydrogenase sensitizes cisplatin-resistant cells to death
author_facet	Catanzaro, Daniela Gaude, Edoardo Orso, Genny Giordano, Carla Guzzo, Giulia Rasola, Andrea Ragazzi, Eugenio Caparrotta, Laura Frezza, Christian Montopoli, Monica
author_sort	Catanzaro, Daniela
title	Inhibition of glucose-6-phosphate dehydrogenase sensitizes cisplatin-resistant cells to death
title_short	Inhibition of glucose-6-phosphate dehydrogenase sensitizes cisplatin-resistant cells to death
title_full	Inhibition of glucose-6-phosphate dehydrogenase sensitizes cisplatin-resistant cells to death
title_fullStr	Inhibition of glucose-6-phosphate dehydrogenase sensitizes cisplatin-resistant cells to death
title_full_unstemmed	Inhibition of glucose-6-phosphate dehydrogenase sensitizes cisplatin-resistant cells to death
title_sort	inhibition of glucose-6-phosphate dehydrogenase sensitizes cisplatin-resistant cells to death
description	The mechanisms of cisplatin resistance, one of the major limitations of current chemotherapy, has only partially been described. We previously demonstrated that cisplatin-resistant ovarian cancer cells (C13), are characterized by reduced mitochondrial activity and higher glucose-dependency when compared to the cisplatin-sensitive counterpart (2008). In this work we further characterized the role of metabolic transformation in cisplatin resistance. By using transmitochondrial hybrids we show that metabolic reprogramming of cisplatin-resistant cell is not caused by inherent mtDNA mutations. We also found that C13 cells not only present an increased glucose-uptake and consumption, but also exhibit increased expression and enzymatic activity of the Pentose Phosphate pathway (PPP) enzyme Glucose-6-Phosphate Dehydrogenase (G6PDH). Moreover, we show that cisplatin-resistant cells are more sensitive to G6PDH inhibition. Even if the metabolomic fingerprint of ovarian cancer cells remains to be further elucidated, these findings indicate that PPP offers innovative potential targets to overcome cisplatin resistance.
publisher	Impact Journals LLC
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4745784/
_version_	1613535568253157376

Inhibition of glucose-6-phosphate dehydrogenase sensitizes cisplatin-resistant cells to death

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