Tryptamine is an endogenous neuroactive metabolite of
tryptophan. Interpretation of the function of this bioamine, however, is restricted to manipulation with
tryptamine synthetic pathways. Meanwhile,
tryptamine is a potent inhibitor of protein biosynthesis, via the competitive inhibition of
tryptophanyl-tRNA synthetase (TrpRS). The influence of the persistent
tryptamine inhibition on the half-life and cellular content of TrpRS was examined by chase labeling of HeLa cells and the
tryptamine-resistant subline with [35S]
methionine. The results indicate that long-term
tryptamine treatment of HeLa cells led to a significant increase in the half-life of TrpRS while the content, in vivo phosphorylation and gene dose of TrpRS were unchanged. These findings suggest that survival of
drug-resistant cells may not be due to TrpRS gene amplification, but to stabilization of TrpRS. It was shown that
tryptamine is an effective inhibitor of HeLa cell growth. In contrast to the well-characterized
antineoplastic compounds, conferring a many hundred-fold elevated drug resistance to
tumor cells, resistance to
tryptamine at very low levels was difficult to achieve, i.e. the 2-fold resistant subline was selected after 19 months of treatment of HeLa cells with gradually increasing concentrations of
tryptamine. The
tryptamine-resistant HeLa subline exhibited a slower growth rate than the original HeLa line when similar concentrations of both cell populations were seeded on the plates. A low
tryptamine resistance and a lack of TrpRS gene amplification were observed in two
tryptamine-resistant HeLa sublines and three Chinese hamster sublines. The role of TrpRS in
oncogenesis and the perspective for
tryptamine as a potential anti-
cancer drug are discussed.