Comparative in vitro biological evaluation of daunorubicin containing GnRH-I and GnRH-II conjugates developed for tumor targeting

Ildikõ Szabõ, Szilvia Bosze, Erika Orbán, Éva Sipos, Gábor Halmos, Magdolna Kovács, Gábor Mezo

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Hormone based drug targeting is a promising tool for selective tumor therapy. In this study, synthesis and systematic comparative biological evaluation of novel drug containing analogs of gonadotropin-releasing hormone GnRH-I and GnRH-II is reported demonstrating their suitability for tumor targeting. The cytotoxic conjugates were prepared by the attachment of the chemotherapeutical agent daunorubicin (Dau) to GnRH analogs directly or through an enzyme-labile spacer with oxime linkage. All conjugates were found to be proteolytically stable under circumstances applied in biological assays. Both GnRH-I and GnRH-II were able to bind similarly to high-affinity GnRH-I receptors on human pituitary and human prostate cancer cells. The in vitro long-term cytotoxic effect of the conjugates was comparable with that of the free drug in human breast and colon cancer cell lines. Furthermore, a concentration-dependent cellular uptake profile was observed. The in vitro apoptotic effect of the compounds was evaluated by flow cytometry analysis using annexin-V. Our results show that both the GnRH-I and the GnRH-II based analogs might be applied for targeted tumor therapy.

Original languageEnglish
Pages (from-to)426-435
Number of pages10
JournalJournal of Peptide Science
Volume21
Issue number5
DOIs
Publication statusPublished - May 1 2015

Keywords

  • apoptotic effect
  • gonadotropin-releasing hormone
  • long-term cytotoxic effect
  • receptor binding affinity
  • targeted tumor therapy
  • targeting unit

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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