Rewiring carbohydrate catabolism differentially affects survival of pancreatic cancer cell lines with diverse metabolic profiles
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Tiziana Tataranni1, Francesca Agriesti1, Vitalba Ruggieri1, Carmela Mazzoccoli1, Vittorio Simeon1, Ilaria Laurenzana1, Rosella Scrima2, Valerio Pazienza3, Nazzareno Capitanio2 and Claudia Piccoli1,2
1Laboratory of Pre-Clinical and Translational Research, IRCCS CROB, Referral Cancer Center of Basilicata, Rionero in Vulture, Italy
2Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy
3Gastroenterology Unit, IRCCS “Casa Sollievo della Sofferenza”, Hospital San Giovanni Rotondo (FG), Foggia, Italy
Claudia Piccoli, email: email@example.com
Keywords: metabolic profiling, pancreatic cancer, mitochondrial metabolism, oxidative stress, metabolic therapy
Received: November 02, 2016 Accepted: March 15, 2017 Published: April 17, 2017
An increasing body of evidence suggests that targeting cellular metabolism represents a promising effective approach to treat pancreatic cancer, overcome chemoresistance and ameliorate patient’s prognosis and survival. In this study, following whole-genome expression analysis, we selected two pancreatic cancer cell lines, PANC-1 and BXPC-3, hallmarked by distinct metabolic profiles with specific concern to carbohydrate metabolism. Functional comparative analysis showed that BXPC-3 displayed a marked deficit of the mitochondrial respiratory and oxidative phosphorylation activity and a higher production of reactive oxygen species and a reduced NAD+/NADH ratio, indicating their bioenergetic reliance on glycolysis and a different redox homeostasis as compared to PANC-1. Both cell lines were challenged to rewire their metabolism by substituting glucose with galactose as carbon source, a condition inhibiting the glycolytic flux and fostering full oxidation of the sugar carbons. The obtained data strikingly show that the mitochondrial respiration-impaired-BXPC-3 cell line was unable to sustain the metabolic adaptation required by glucose deprivation/substitution, thereby resulting in a G2\M cell cycle shift, unbalance of the redox homeostasis, apoptosis induction. Conversely, the mitochondrial respiration-competent-PANC-1 cell line did not show clear evidence of cell sufferance. Our findings provide a strong rationale to candidate metabolism as a promising target for cancer therapy. Defining the metabolic features at time of pancreatic cancer diagnosis and likely of other tumors, appears to be crucial to predict the responsiveness to therapeutic approaches or coadjuvant interventions affecting metabolism.
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