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Harrison Boldizasr, Bela Szende, Ferenc Timar
Med Sci Monit 1999; 5(6): BR1059-1064
K 562 human leukemia cells and HT 168 melanoma cells were cultured for 72 hours in Minimal Essential Medium (MEM) with or without asparagine. (AspNH2) and supplemented with 2.6 mmol/l glycine (Gly), 1.9 mmol/l gamma amino butyric acid (GABA), 1.5 mmol/l aspartic acid (Asp) or 6.8 mmol/l glutamic acid (Glu). Gly significantly inhibited the proliferation of both types of tumor cells both in the presence and the absence of AspNH2. This inhibitory effect developed gradually, usually by the 48th hour of incubation. Some of the Gly-treated cells showed signs indicative of apoptosis. In AspNH2-free MEM both the control and the experimental cell groups (supplemented with Gly, GABA, Asp or Glu) showed much slower proliferation than in MEM containing AspNH2. The values obtained in GABA-supplemented MEM in 72 hour experiment did not differ significantly from the control. Glu and Asp induced a significant rise in the growth of leukemia cells by the 3rd day of incubation. The growth of melanoma cells in Glu- or Asp-containing MEM did not significantly
differ from the control but significantly exceeded the value obtained in MEM supplemented with Gly. It is supposed that Cl-transport into tumor cells decreases and Na+ transport increases as a result of changes in the extracellular/intracellular ratio of excitatory/inhibitory amino acids. This results in depolarization which maintains cell division. The results suggest that some non-essential, transmitter amino acids exert either inhibitory or stimulating effect on tumor cell proliferation. This finding may open up new possibilities in preventing tumor growth.