Abstract #1215: The protective role of 2-Deoxy-D-Glucose (2DG) against high-dose chemotherapy induced toxicity

Caloric restriction (CR) has been reported to increase lifespan in many species. Short-term starvation or low glucose could protect mammalian cells against high dose of chemotherapy. 2-Deoxy-D-Glucose (2DG) is a synthetic glucose analog that inhibits intracellular utilization of glucose and inhibits ATP synthesis. 2DG has been used as a CR mimetic compound that reduces the energy availability at the cellular level and provides protection from radiotherapy, excitotoxicity and cardiovascular risk factors. The purpose of this study is to investigate whether 2DG, particularly with oral administration, can protect animals against the toxicity induced by high dose chemotherapy. Female nude mice were used in the study. The maximum dose of chemotherapeutic agents was determined to be that producing 20% animal body weight loss and not causing drug related lethality. Animals were dosed with Docetaxel (40mg/kg, iv) or Cisplatin (10mg/kg, iv) alone or in combination with 2DG (500 to 2000mg/kg, po). All drugs were administered on Day 1 and Day 8. Body weight (BW) was monitored daily and hematological toxicity was examined on Day 14. The BW loss was 12.4% on Day 14 in the Docetaxel alone group and in 1 of 5 mice the BW loss was more than 20%. 2DG 500mg/kg and 1000mg/kg in combination with Docetaxel showed 5.7% and 8.3% BW decrease respectively. No animals lost more than 20% weight in the 2DG groups. Increasing the dose of 2DG to 2000mg/kg did not enhance the protective activity. Cisplatin alone gave 9.6% BW loss on Day 11, while only a loss of 1.4% was observed when 2DG 1000mg/kg was combined with the Cisplatin. Hematologically, Docetaxel alone significantly decreased white blood cells (WBC), 3.4 ± 0.5 vs 6.0 ± 0.6 in Vehicle (p Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1215.