Inhibition of glucose-6-phosphate dehydrogenase sensitizes cisplatin-resistant cells to death
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Catanzaro, D., Gaude, E., Orso, G., Giordano, C., Guzzo, G., Rasola, A., Ragazzi, E., et al. (2015). Inhibition of glucose-6-phosphate dehydrogenase sensitizes cisplatin-resistant cells to death. Oncotarget, 6 30102-30114. https://doi.org/10.18632/oncotarget.4945
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 cisplatinsensitive 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.
cisplatin, drug resistance, cancer metabolism, PPP, transmitochondrial hybrids
This work was financially supported by PRAT (University of Padova), grant no. CPDA124517/12 and MIUR grant no 60A04–0443. DC fellowship was supported by grant no. CPDR134012. AR was supported by the AIRC grant no. IG 15863 and by the University of Padova grant no. CPDA 123598.
Medical Research Council (MC_UU_12022/6)
External DOI: https://doi.org/10.18632/oncotarget.4945
This record's URL: https://www.repository.cam.ac.uk/handle/1810/253793
Attribution 2.0 UK: England & Wales
Licence URL: http://creativecommons.org/licenses/by/2.0/uk/
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