In-vivo antitumour effect of daunorubicin-GnRH-III derivative conjugates on colon carcinoma-bearing mice

Marilena Manea, József Tóvári, Miguel Tejeda, Ákos Schulcz, Bence Kapuvári, Borbála Vincze, Gábor Mezo

Research output: Article

17 Citations (Scopus)

Abstract

Targeted cancer chemotherapy is a novel approach developed for the specific delivery of anticancer drugs. Tumour targeting can be achieved by combining a chemotherapeutic agent with a targeting moiety that recognizes tumour-specific or highly expressed receptors on cancer cells. We used the gonadotropin- releasing hormone-III (GnRH-III) as a targeting moiety to which the chemotherapeutic agent daunorubicin (Dau) was attached through an oxime bond either directly or by inserting a GFLG tetrapeptide spacer. The in-vivo toxicity of Dau-GnRH-III derivative conjugates was evaluated on healthy BDF-1 female mice, and their tumour growth inhibitory effect was determined on C26 murine and HT-29 human colon carcinoma-bearing mice. Both oxime bond-containing conjugates were well tolerated and exerted significant antitumour activity on C26 colon carcinoma-bearing mice at a dose of 30 mg Dau content in conjugate/kg body weight. Furthermore, the conjugates inhibited the tumour growth more than the free drug at a dose that was still not toxic. Similar tumour growth inhibitory effects were obtained on HT-29 human colon carcinoma-bearing mice using three treatments with 15 mg Dau content in conjugate/kg. The tumour growth inhibitions according to the tumour volume and the tumour weight were 44/41% and 58/50%, respectively. Considering the results, both of the investigated Dau-GnRH-III derivative conjugates were well tolerated and had significant antitumour effect on colon carcinoma-bearing mice.

Original languageEnglish
Pages (from-to)90-97
Number of pages8
JournalAnti-Cancer Drugs
Volume23
Issue number1
DOIs
Publication statusPublished - jan. 1 2012

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Cancer Research

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