Studies on the anti-tumour activity of aliphatic aldehydes — I: The mechanism of inhibition of amino acid incorporation into protein of Yoshida ascites hepatoma cells

Abstract

A number of 2-, 3- and 4-carbon aliphatic aldehydes have been shown to depress the aerobic incorporation of labelled leucine into protein of Yoshida ascites hepatoma cells, at a concentration which does not appreciably affect respiration. Inhibition of anaerobic amino acid incorporation was also observed. Under these conditions, the inhibitory effect was lower than aerobically, except for aldehydes which strongly depressed glucose metabolism. Potentiometric and manometric measurements showed that aliphatic aldehydes condense with the amino acid cysteine and this result has been confirmed following the disappearance of free SH-groups from solutions of cysteine after the addition of aldehydes. The condensation product had the chromatographic R f of the corresponding thiazolidine- 4-carboxylic acid. l-Cysteine, added in vitro prior to the addition of aldehydes, prevented their inhibitory effects on glycolysis and amino acid incorporation into protein of Yoshida ascites tumour cells. Other amino acids were completely ineffective. Cysteine also relieved, at least in part, previously established inhibitions. Thiazolidine- 4-carboxylic acids did not affect glycolysis and had only a minor effect on protein synthesis. A C 14 -labelled thiazolidine- 4-carboxylic acid (from C 14 -α,β-dihydroxy-butyraldehyde) was not incorporated into protein of ascites hepatoma cells. These results and the possibility that thiazolidine carboxylic acids can be formed at the expense of endogenous cysteine suggest that a decrease in the intracellular concentration of this SH-amino acid may be regarded as the primary step in the inhibition of protein synthesis by aliphatic aldehydes.