Inhibition of methionine uptake by methotrexate in mouse leukemia L1210 cells

Abstract
Summary Methionine-auxotrophic L1210 cells were used to study the effect of methotrexate (MTX) on methionine utake and metabolism. MTX was shown to inhibit amino acid transport systems and cause a decrease of methionine uptake into L1210 cells. Conversely, a nonmetabolizable amino acid analogue reduced MTX uptake into L1210 cells. MTX also blocked the transfer of the beta carbon from serine into methionine. Therefore, methionine deprivation may be an additional mechanism of action for MTX in methionine-auxotrophic tumor cells.