Lung cancer is the leading cause of cancer related deaths in the US with an expected 228,000 new cases diagnosed per year. Lung tumor cells are reported to glutamine (Gln) and excrete glutathione (GSH), suggesting actively utilize the γ-glutamyl cycle. Once GSH is excreted from the tumor cells, GSH is hydrolyzed or used to form γ-glutamyl-amino-acids. The function of extracellular GSH and γ-glutamyl-amino-acids are still unclear. Glutamine, a precursor to GSH, is known to induce transformations in the NIH-3T3 cell line. Therefore, it was hypothesized the GSH and γ-glutamyl-glutamine would induce transformation in the NIH-3T3 cells. Treatment of the cells with 5mM Gln induced transformation, and thus confirmed the importance of Gln in inducing transformation in the NIH-3T3 cells. Treatment of the NIH-3T3 cells with γ-glutamylglutamine (0.01, 0.1, 1, 2.5, or 5mM) lead to a linear increase in transformations up to 2.5mM before decreasing at the highest concentration studied. These results provide evidence for γ-glutamylglutamine’s ability to induce transformation in the normal cells. In contrast, GSH by itself does not induce transformations. Treatment with γ-glutamylglutamine plus glutamine did not show any increase in transformations compared to those induced by glutamine alone, suggesting that these compounds work by the same mechanism. Together, these results indicate that if malignant lung tumor cells migrate to normal tissue, excrete GSH, and produce γ-glutamylglutamine, the may initiate transformation in the normal tissue producing a heterogeneous metastasis.

Effect of glutamine and γ-glutamylglutamine on NIH-3T3 cell metabolism

253rd National Meeting (2017)

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