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

Daniela Catanzaro, Edoardo Gaude, Genny Orso, Carla Giordano, Giulia Guzzo, Andrea Rasola, Eugenio Ragazzi, Laura Caparrotta, Christian Frezza, Monica Montopoli

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)30102-30114
Number of pages13
JournalOncotarget
Volume6
Issue number30
DOIs
Publication statusPublished - 2015

Keywords

  • Cancer metabolism
  • Cisplatin
  • Drug resistance
  • PPP
  • Transmitochondrial hybrids

ASJC Scopus subject areas

  • Oncology

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    Catanzaro, D., Gaude, E., Orso, G., Giordano, C., Guzzo, G., Rasola, A., Ragazzi, E., Caparrotta, L., Frezza, C., & Montopoli, M. (2015). Inhibition of glucose-6-phosphate dehydrogenase sensitizes cisplatin-resistant cells to death. Oncotarget, 6(30), 30102-30114. https://doi.org/10.18632/oncotarget.4945