Deuterium Depletion Inhibits Cell Proliferation, RNA and Nuclear Membrane Turnover to Enhance Survival in Pancreatic Cancer

• Published in: Cancer control 2021-01, Vol.28, p.1073274821999655-1073274821999655
• Main Authors: Boros, László G., Somlyai, Ildikó, Kovács, Beáta Zs, Puskás, László G., Nagy, Lajos I., Dux, László, Farkas, Gyula, Somlyai, Gábor
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Cell Proliferation; Chemotherapy; Deuterium - pharmacology; Deuterium - therapeutic use; Female; Gastric cancer; Glucose; Growth rate; Humans; Male; Membrane turnover; Mitochondria; Nuclear Envelope - drug effects; Original; Pancreatic cancer; Pancreatic Neoplasms; Pancreatic Neoplasms - genetics; Patients; Ribose; RNA - drug effects; Statistical analysis
• ISSN: 1073-2748; 1526-2359; 1073-2748
• DOI: 10.1177/1073274821999655

The effects of deuterium-depleted water (DDW) containing deuterium (D) at a concentration of 25 parts per million (ppm), 50 ppm, 105 ppm and the control at 150 ppm were monitored in MIA-PaCa-2 pancreatic cancer cells by the real-time cell impedance detection xCELLigence method. The data revealed that lower deuterium concentrations corresponded to lower MiA PaCa-2 growth rate. Nuclear membrane turnover and nucleic acid synthesis rate at different D-concentrations were determined by targeted [1,2-13C2]-D-glucose fate associations. The data showed severely decreased oxidative pentose cycling, RNA ribose 13C labeling from [1,2-13C2]-D-glucose and nuclear membrane lignoceric (C24:0) acid turnover. Here, we treated advanced pancreatic cancer patients with DDW as an extra-mitochondrial deuterium-depleting strategy and evaluated overall patient survival. Eighty-six (36 male and 50 female) pancreatic adenocarcinoma patients were treated with conventional chemotherapy and natural water (control, 30 patients) or 85 ppm DDW (56 patients), which was gradually decreased to preparations with 65 ppm and 45 ppm deuterium content for each 1 to 3 months treatment period. Patient survival curves were calculated by the Kaplan-Meier method and Pearson correlation was taken between medial survival time (MST) and DDW treatment in pancreatic cancer patients. The MST for patients consuming DDW treatment (n = 56) was 19.6 months in comparison with the 6.36 months’ MST achieved with chemotherapy alone (n = 30). There was a strong, statistically significant Pearson correlation (r = 0.504, p < 0.001) between survival time and length and frequency of DDW treatment.