TY  - JOUR
A1  - Voß, Martin
A1  - Lorenz, Nadja Irene
A1  - Luger, Anna-Luisa
A1  - Steinbach, Joachim Peter
A1  - Rieger, Johannes
A1  - Ronellenfitsch, Michael Wilfried
T1  - Rescue of 2-Deoxyglucose side effects by ketogenic diet
T2  - International journal of molecular sciences
N2  - Cancer metabolism is characterized by extensive glucose consumption through aerobic glycolysis. No effective therapy exploiting this cancer trait has emerged so far, in part, due to the substantial side effects of the investigated drugs. In this study, we examined the side effects of a combination of isocaloric ketogenic diet (KD) with the glycolysis inhibitor 2-deoxyglucose (2-DG). Two groups of eight athymic nude mice were either fed a standard diet (SD) or a caloric unrestricted KD with a ratio of 4 g fat to 1 g protein/carbohydrate. 2-DG was investigated in commonly employed doses of 0.5 to 4 g/kg and up to 8 g/kg. Ketosis was achieved under KD (ketone bodies: SD 0.5 ± 0.14 mmol/L, KD 1.38 ± 0.28 mmol/L, p < 0.01). The intraperitoneal application of 4 g/kg of 2-DG caused a significant increase in blood glucose, which was not prevented by KD. Sedation after the 2-DG treatment was observed and a behavioral test of spontaneous motion showed that KD reduced the sedation by 2-DG (p < 0.001). A 2-DG dose escalation to 8 g/kg was lethal for 50% of the mice in the SD and for 0% of the mice in the KD group (p < 0.01). A long-term combination of KD and an oral 1 or 2 g 2-DG/kg was well-tolerated. In conclusion, KD reduces the sedative effects of 2-DG and dramatically increases the maximum tolerated dose of 2-DG. A continued combination of KD and anti-glycolytic therapy is feasible. This is, to our knowledge, the first demonstration of increased tolerance to glycolysis inhibition by KD.
KW  - 2-deoxyglucose (2-DG)
KW  - isocaloric ketogenic diet
KW  - glycolysis
KW  - Warburg effect
KW  - metabolic cancer therapy
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/47145
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-471455
SN  - 1422-0067
SN  - 1661-6596
N1  - This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
VL  - 19
IS  - 8, Art. 2462
SP  - 1
EP  - 12
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  -