Novel antitumor peptide hormones and their effect on signal transduction

J Steroid Biochem Mol Biol. 1992 Sep;43(1-3):105-10. doi: 10.1016/0960-0760(92)90193-m.

Abstract

A series of novel gonadotropin releasing hormone (GnRH) and Somatostatin analogs have been developed in our laboratory and were screened for antiproliferative and signal transduction inhibitory effect. Our GnRH analog Folligen, had significant antitumor activity on DMBA induced mammary carcinomas in rats without blocking ovarian functions. The direct effect of Folligen and Buserelin has been compared on the human breast cancer cell line MDA-MB-231. Folligen was found to be more effective in inhibiting cell proliferation and significant differences were found in the signal transduction pathways activated by these analogs. Our novel Somatostatin analogs were screened for tyrosine kinase inhibition and for antiproliferative effect on human colon tumor cells and for growth hormone (GH) release inhibition in vitro and in vivo. The analog TT-2-50 was significantly more active inhibiting GH release in superfused rat pituitary cells and in vivo than native Somatostatin and it strongly inhibited tyrosine kinase and proliferation while it stimulated protein kinase C activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms
  • Buserelin / analogs & derivatives
  • Buserelin / pharmacology
  • Cell Division / drug effects
  • Colonic Neoplasms
  • Drug Screening Assays, Antitumor
  • Female
  • Gonadotropin-Releasing Hormone / analogs & derivatives*
  • Gonadotropin-Releasing Hormone / pharmacology
  • Goserelin
  • Humans
  • Molecular Sequence Data
  • Peptides / pharmacology
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Rats
  • Rats, Inbred Strains
  • Signal Transduction / drug effects*
  • Somatostatin / analogs & derivatives*
  • Somatostatin / pharmacology
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Peptides
  • Goserelin
  • folligen
  • ovurelin
  • Gonadotropin-Releasing Hormone
  • Somatostatin
  • Protein-Tyrosine Kinases
  • Buserelin