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 microM, 200 microM, and 0 microM] 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 microM and 0 microM glutamine). Glutamine deprivation resulted in a significant decrease in glutathione levels by 20% compared with control, but glutathione in 0 microM glutamine was maintained with the same levels found in 400 microM and 200 microM 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.