HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Tryptamine-mediated stabilization of tryptophanyl-tRNA synthetase in human cervical carcinoma cell line.

Abstract
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.
AuthorsE L Paley
JournalCancer letters (Cancer Lett) Vol. 137 Issue 1 Pg. 1-7 (Mar 22 1999) ISSN: 0304-3835 [Print] Ireland
PMID10376788 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Tryptamines
  • tryptamine
  • Tryptophan-tRNA Ligase
Topics
  • Animals
  • Cell Division (drug effects)
  • Cell Line
  • Cricetinae
  • Cricetulus
  • Drug Resistance
  • Female
  • Gene Amplification
  • Half-Life
  • HeLa Cells (cytology, drug effects)
  • Humans
  • Phosphorylation
  • Tryptamines (pharmacology)
  • Tryptophan-tRNA Ligase (antagonists & inhibitors, drug effects, genetics)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: