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Glucose restriction, ketone supplementation, and hyperbaric oxygen therapy inhibit proliferation and viability and increase reactive oxygen species production in VM‐M3 glioma cells (644.18)
Author(s) -
Poff Angela,
D'Agostino Dominic
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.644.18
Subject(s) - warburg effect , reactive oxygen species , ketone bodies , trypan blue , cancer cell , viability assay , chemistry , medicine , pharmacology , apoptosis , cancer , biochemistry , metabolism
The Warburg Effect and tumor hypoxia underlie a unique cancer metabolism characterized by glucose dependency and mitochondrial dysfunction. Previous research indicates this phenotype can be exploited therapeutically with glucose restriction, ketone supplements, or hyperbaric oxygen (HBOT). We have previously shown that these conditions decrease tumor growth and metastatic spread and increase survival time in mice with VM‐M3 metastatic cancer. To further characterize the effects of these therapies, we measured proliferation, viability, and ROS production in VM‐M3 cells exposed to these conditions: high glucose (control; 25mM), low glucose (LG; 3mM), ketone supplementation (βHB; 5mM), hyperbaric oxygen (HBOT; 90 min, 2.5 ATA), or combination therapy (LG+BHB+HBOT). Proliferation of VM‐M3 cells was measured with trypan blue hemocytometry and was significantly decreased from controls at 24, 48, 72, and 96 hours (p<05). Viability of VM‐M3 cells was measured by fluorescence microscopy with calcein and EthD‐1 and was decreased by 19.2% in LG, 12.5% in βHB, and 38.2% in LG+βHB+HBOT treated cells compared to control (p<0.05). ROS production was measured by fluorescent microscopy with DHE and was increased by 46% in HBOT and by 48% in LG+βHB+HBOT treated cells compared to control (p<0.001). This study further supports the use of these metabolic therapies as a potential cancer treatment. Grant Funding Source : Supported by Office of Naval Research and a charitable donation from Scivation Inc.