Influence on antiproliferative activity of structural modification and conjugation of gonadotropin-releasing hormone (GnRH) analogues

A. Kálnay, I. Pályi, B. Vincze, R. Mihalik, I. Mezõ, J. Pató, J. Seprõdi, S. Lovas, R. F. Murphy

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12 Citations (Scopus)

Abstract

The effect of various GnRH analogues, and their conjugates on proliferation, clonogenicity and cell cycle phase distribution of MCF-7 and Ishikawa human cancer cell lines was studied. GnRH-III, a sea lamprey GnRH analogue reduced cell proliferation by 35% and clonogenicity by 55%. Structural modifications either decreased, or did not alter biological activity. Conjugation of GnRH analogues including MI-1544, MI-1892, and GnRH-III with poly(N-vinylpyrrolidone-co-maleic acid) (P) through a tetrapeptide spacer GFLG(X) substantially increased the inhibitory effect of the GnRH analogues. The conjugate P-X-GnRH-III induced significant accumulation of cells in the G2/M phase; from 8% to 15.6% at 24 h and 9.8% to 15% at 48 h. It was concluded that conjugation of various GnRH analogues substantially enhanced their antiproliferative activity, strongly reduced cell clonogenicity and retarded cell progression through the cell division cycle at the G2/M phase.

Original languageEnglish
Pages (from-to)275-285
Number of pages11
JournalCell Proliferation
Volume33
Issue number5
DOIs
Publication statusPublished - Nov 13 2000

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Keywords

  • Antiproliferative activity
  • Cell cycle effect
  • GnRH analogues
  • GnRH conjugates
  • Human cancer cell line

ASJC Scopus subject areas

  • Cell Biology

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