EFFECT OF METHIONINE ON GLYCOLYSIS IN TUMOR-CELLS - IN-VIVO AND IN-VITRO NMR-STUDIES

Inhibition of glycolysis by methionine is a phenomenon previously show n in transformed cells growing in culture, In a recent paper, [Collet V. et al., Q, Magn. Res. Biol. Med. 11, 127-134 (1995)] we investigate d this effect in vivo by C-13 nuclear magnetic resonance spectroscopy, but the results did not clearly support this hypothesis. In this work , in vivo C-13 NMR spectroscopy has been performed on tumors developin g in nude mice following the injection of two types of cells establish ed in culture, (1) rat kidney cells transformed by Kirsten murine sarc oma virus, (NRK-K), i.e. the same tumor cell line as that used in the original paper; and (2) a n ell dedifferentiated human prostate adenoc arcinoma cell line (PC3), Furthermore, in vitro experiments were perfo rmed with the same tumor cell lines, The effect of methionine on glyco lysis was assayed by biochemical monitoring of lactate production in t he supernatant of these cells grown in vitro. Lastly, H-1 in vitro NMR spectroscopy of the PC3 line performed on perchloric extracts of both supernatants and cells growing in the presence of (1-C-13) glucose, a llowed simultaneous detection of glucose and lactate as well as estima tion of the lactate-specific enrichment, The ill vitro experiments con firmed the inhibiting effect of methionine on glycolysis and demonstra ted the absence of a significant modification of the pentose phosphate pathway activity by this aminoacid, In contrast, none of the in vivo experimental results were compatible with this phenomenon, which is pr obably affected by more general physiological events.