Glutamine regulates amino acid transport and glutathione levels in a human neuroblastoma cell line

Both amino acid transport and glutathione play a key role in regulating cancer cell growth. Glutamine can serve as an important ATP source for cancer cells, and it can supply glutamate, a precursor for the synthesis of glutathione, by the hydrolysis of glutamine. We examined the effects of glutamine concentrations [ 2 mM ( control), 400 muM, 200 muM, and 0 muM] on cell growth, amino acid transport, and glutathione levels in a human neuroblastoma cell line, SK-N-SH, by using cell culture technique. Cell growth rates were dependent on glutamine concentrations in culture media. Glutamate transport significantly increased in glutamine-deprived groups, and this increase was remarkable in lower glutamine groups ( 200 muM and 0 muM glutamine). Glutamine deprivation resulted in a significant decrease in glutathione levels by 20% compared with control, but glutathione in 0 muM glutamine was maintained with the same levels found in 400 muM and 200 muM glutamine. DNA and protein synthesis correlated directly with glutamine concentrations in culture media. Our results suggest that glutamine mediates neuroblastoma cell proliferation by regulating amino acid transport and glutathione synthesis, both when sufficient nutrients are present and when key nutrients such as glutamine are in limited supply.