Abstract 81: Differential metabolic and viability responses of the A549 and MRC-5 cell lines upon exposure to selective organic inhibitors of glycolysis

Abstract

Abstract Lung cancer is a one of the most prevalent and deadly cancers in United States. Research has shown that cancer cells exhibit higher glycolytic rates than normal cells. Studies on the differential role of the interference with glycolysis/energy generation by cancer cells through the use natural glycolytic inhibitors were limited in the literature. Therefore, we hypothesize that exposure of lung cancer cells to natural inhibitors of glycolysis will negatively influence their metabolic activities as well as their cell viabilities due to the inhibition of substrate-level ATP generation, while differentially not affecting the normal lung phenotype. The human lung fibroblast cell line (MRC-5) was selected to represent the normal human lung and the human alveolar epithelial cell line A549 was selected to represent lung cancer in vitro. These cells were maintained and exposed to eleven different organic reagents including fructose diphosphate (FDP), sodium citrate, ascorbic acid, crude honey, sodium bicarbonate, D-glucose, oxalic acid, glycerol, zinc acetate, pyruvic acid, and sodium ascorbate at concentration levels ranging from 31.3-2,000 ug/ml for 24-72 hours in 5% CO2 and 96 well plates using MTT, Alamar blue and the T4 cellometer assays as well as phase-contrast photo-imaging. Our results indicate that exposure of A549 cells to these organics resulted in concentration dependent differential cell destruction of the A549 cell line. Nine of the eleven organics used showed statistically significant (p<0.05) differential negative effects (impaired metabolic activity and cell death) on the A549 cell line in comparison to its control as well as to their effects on the MRC-5 cell line using MTT, Alamar blue and T4 cell viability assays. Data from the MTT assay showed limitations in detecting the true cell viability in comparison to the T4 data. Viability using the T4 cellometer ranged between 60-76% for the A549 compared to 96-100% for its control as well as the exposed MRC-5 cell line. LC50 using MTT and Alamar blue assays ranged between 161-1041 ug/ml. None of the eleven chemicals used allowed for cell proliferation of the A549 cell line while showing no or minor effects on the MRC-5 cell line. We conclude that nine of the tested organics impaired glycolysis, which is crucial to the generation of cellular energy and survival of the A549 cell line. Supported by NIH-RCMI grant# G12RR13459 and NIH-RISE grant # 63228. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 81.