Unique antitumour effects of L-2,4 diaminobutyric acid on cultured hepatoma cells.
A single hepatoma cell line was grown in vitro and incubated with L-2,4 diaminobutyric acid (DAB), a non-metabolizable amino acid, under various conditions. The tumour cells were irreversibly damaged by incubation for 8 hours with 8 mmol/L of DAB. The tumour cell-destroying effect of DAB was dose- and time-dependent with no effect at a DAB concentration of 1.6 mmol/L. The presence of N-methyl alpha-aminoisobutyric acid (a specific substrate of amino acid transport system A) in the incubation medium abrogated the tumour cell destructive effect of DAB in a dose-dependent fashion. The presence of non-physiological amino acids in the incubation medium per se was not the cause of tumour cell destruction, since inclusion of alpha-amino-isobutyric acid and N-methyl alpha-aminoisobutyric acid in the incubation medium did not influence the viability of hepatoma cells. We conclude that the tumour cell destructive effect of DAB was the result of a huge and unlimited uptake of DAB energized by the Na(+)-gradient and that this uptake was not subjected to the law of saturation kinetics. This was combined with a tumour cell energy crisis in attempts to restore the Na(+)-gradient.
Blind
Per-Jonas
PJ
Department of Surgery, University Hospital, Lund University, SE-221 45 Lund, Sweden.
Waldenström
Anders
A
Hafström
Larsolof
L
Berggren
Diana
D
Ronquist
Gunnar
G
D000613:Aminobutyrates / Q000494:pharmacology*; D000621:Aminoisobutyric Acids / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001692:Biological Transport; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D004734:Energy Metabolism; D017136:Ion Transport; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D012964:Sodium / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000613:Aminobutyrates; D000621:Aminoisobutyric Acids; D000970:Antineoplastic Agents; C100049:2-aminoisobutyric acid; C017911:2-(methylamino)isobutyric acid; C005959:2,4-diaminobutyric acid; D012964:Sodium