Improved in vivo anti-tumor and anti-metastatic effect of GnRH-III-daunorubicin analogs on colorectal and breast carcinoma bearing mice

Ivan Randelovic, Sabine Schuster, Bence Kapuvári, Gianluca Fossati, Christian Steinkühler, Gábor Mezo, József Tóvári

Research output: Contribution to journalArticle

2 Citations (Scopus)


Among various homing devices, gonadotropin-releasing hormone-III (GnRH-III) peptide represents a suitable targeting moiety for drug delivery systems. The anti-tumor activity of the previously developed GnRH-III-[4Lys(Bu),8Lys(Dau=Aoa)] conjugate and the novel synthesized GnRH-III-[2δHis,3D-Tic,4Lys(Bu),8Lys(Dau=Aoa)] conjugate, containing the anti-cancer drug daunorubicin, were evaluated. Here, we demonstrate that both GnRH-III-Dau conjugates possess an efficient growth inhibitory effect on more than 20 cancer cell lines, whereby the biological activity is strongly connected to the expression of gonadotropin-releasing hormone receptors (GnRH-R). The novel conjugate showed a higher in vitro anti-proliferative activity and a higher uptake capacity. Moreover, the treatment with GnRH-III-Dau conjugates cause a significant in vivo tumor growth and metastases inhibitory effect in three different orthotopic models, including 4T1 mice and MDA-MB-231 human breast carcinoma, as well as HT-29 human colorectal cancer bearing BALB/s and SCID mice, while toxic side-effects were substantially reduced in comparison to the treatment with the free drug. These findings illustrate that our novel lead compound is a highly promising candidate for targeted tumor therapy in both colon cancer and metastatic breast cancer.

Original languageEnglish
Article number4763
JournalInternational journal of molecular sciences
Issue number19
Publication statusPublished - Oct 1 2019



  • Anti-metastatic activity
  • Cellular uptake
  • Daunorubicin
  • Drug delivery system
  • Gonadotropin releasing hormone III derivates
  • Gonadotropin releasing hormone receptor expression
  • In vitro and in vivo anti-tumor activity
  • Oxime linkage
  • Peptide drug conjugates
  • Targeted cancer therapy

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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