L-Theanine Uptake via Solute Carrier Family 38 Member 1 Inhibits Neuroblastoma Cell Growth

L-gamma-glutamylethylamide (L-theanine, theanine) is an amino acid and an umami component found in green tea. According to previous reports, theanine acts on the central nervous system by alleviating stress and maintaining natural sleep. Furthermore, theanine has been reported to have a mild cancer-suppressing effect. However, the molecular mechanism of theanine's potential central nervous system (CNS) activity remains unclear. We evaluated the inhibitory effect of theanine on the proliferation of neural cell lines and found that theanine most effectively inhibited the proliferation of NSC-34 mouse motor neuron-like hybrid cells compared to other neural cells. NSC-34 cell proliferation inhibition by theanine was completely alleviated by co-administration of α-(methylamino) isobutyric acid or leucine, a substrate of solute carrier family 38 member 1 (Slc38a1, the glutamine transporter) or Slc7a5 (the glutamine/leucine exchanger) respectively. This suggests that theanine uptake into cells occurs via Slc38a1 and excretion from cells occurs via Slc7a5. However, inhibition was observed even in the absence of glutamine and did not correlate with changes in mammalian target of rapamycin phosphorylation levels. These results suggest that theanine inhibits proliferation in a manner that is still unclear after it is taken up into cells. Based on these findings, we propose that theanine may exert an inhibitory effect on the proliferation of neural cells that have abnormally proliferating Slc38a1, namely neuroblastoma.