title: In-vivo antitumour effect of daunorubicin-GnRH-III derivative conjugates on colon carcinoma-bearing mice.
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.
authors.affiliation: Laboratory of Analytical Chemistry and Biopolymer Structure Analysis, Department of Chemistry, University of Konstanz, Konstanz, Germany.
authors.forename: Marilena
authors.initials: M
authors.lastname: Manea
authors.forename: József
authors.initials: J
authors.lastname: Tóvári
authors.forename: Miguel
authors.initials: M
authors.lastname: Tejeda
authors.forename: Akos
authors.initials: A
authors.lastname: Schulcz
authors.forename: Bence
authors.initials: B
authors.lastname: Kapuvári
authors.forename: Borbála
authors.initials: B
authors.lastname: Vincze
authors.forename: Gábor
authors.initials: G
authors.lastname: Mezo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000188:drug therapy*; D003630:Daunorubicin / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D016513:Mice, SCID; D011761:Pyrrolidonecarboxylic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C448022:gonadotropin-releasing hormone-III; D007987:Gonadotropin-Releasing Hormone; D011761:Pyrrolidonecarboxylic Acid; D003630:Daunorubicin