Improved in vivo antitumor effect of a daunorubicin - GnRH-III bioconjugate modified by apoptosis inducing agent butyric acid on colorectal carcinoma bearing mice

Kapuvári, Bence; Hegedüs, Rózsa; Schulcz, Ákos; Manea, Marilena; Tóvári, József; Gacs, Alexandra; Vincze, Borbála; Mező, Gábor

Improved in vivo antitumor effect of a daunorubicin - GnRH-III bioconjugate modified by apoptosis inducing agent butyric acid on colorectal carcinoma bearing mice

Dateien

Kapuvari_0-417644.pdfGröße: 843.75 KBDownloads: 477

Datum

2016

Autor:innen

Kapuvári, Bence

Hegedüs, Rózsa

Schulcz, Ákos

Manea, Marilena

Tóvári, József

Gacs, Alexandra

Vincze, Borbála

Mező, Gábor

Open Access-Veröffentlichung

Open Access Hybrid

Sammlungen

Chemie
Zukunftskolleg

Publikationstyp

Zeitschriftenartikel

Publikationsstatus

Published

Erschienen in

Investigational New Drugs. 2016, 34(4), pp. 416-423. ISSN 0167-6997. eISSN 1573-0646. Available under: doi: 10.1007/s10637-016-0354-7

Zusammenfassung

Compared to classical chemotherapy, peptide-based drug targeting is a promising therapeutic approach for cancer, which can provide increased selectivity and decreased side effects to anticancer drugs. Among various homing devices, gonadotropin-releasing hormone-III (GnRH-III) peptide represents a suitable targeting moiety, in particular in the treatment of hormone independent tumors that highly express GnRH receptors (e.g. colon carcinoma). We have previously shown that GnRH-III[(4)Lys(Ac),(8)Lys(Dau = Aoa)] bioconjugate, in which daunorubicin was attached via oxime linkage to the (8)Lys of a GnRH-III derivative, exerted significant in vivo antitumor effect on subcutaneously developed HT-29 colon tumor. In contrast, results of the study reported here indicated that this compound was not active on an orthotopically developed tumor. However, if Lys in position 4 was acylated with butyric acid instead of acetic acid, the resulting bioconjugate GnRH-III[(4)Lys(Bu),(8)Lys(Dau = Aoa)] had significant tumor growth inhibitory effect. Furthermore, it prevented tumor neovascularization, without detectable side effects. Nevertheless, the development of metastases could not be inhibited by the bioconjugate; therefore, its application in combination with a metastasis preventive agent might be necessary in order to achieve complete tumor remission. In spite of this result, the treatment with GnRH-III[(4)Lys(Bu),(8)Lys(Dau = Aoa)] bioconjugate proved to have significant benefits over the administration of free daunorubicin, which was used at the maximum tolerated dose.

Fachgebiet (DDC)

540 Chemie

Zitieren

ISO 690

KAPUVÁRI, Bence, Rózsa HEGEDÜS, Ákos SCHULCZ, Marilena MANEA, József TÓVÁRI, Alexandra GACS, Borbála VINCZE, Gábor MEZŐ, 2016. Improved in vivo antitumor effect of a daunorubicin - GnRH-III bioconjugate modified by apoptosis inducing agent butyric acid on colorectal carcinoma bearing mice. In: Investigational New Drugs. 2016, 34(4), pp. 416-423. ISSN 0167-6997. eISSN 1573-0646. Available under: doi: 10.1007/s10637-016-0354-7

BibTex

@article{Kapuvari2016Impro-39823,
  year={2016},
  doi={10.1007/s10637-016-0354-7},
  title={Improved in vivo antitumor effect of a daunorubicin - GnRH-III bioconjugate modified by apoptosis inducing agent butyric acid on colorectal carcinoma bearing mice},
  number={4},
  volume={34},
  issn={0167-6997},
  journal={Investigational New Drugs},
  pages={416--423},
  author={Kapuvári, Bence and Hegedüs, Rózsa and Schulcz, Ákos and Manea, Marilena and Tóvári, József and Gacs, Alexandra and Vincze, Borbála and Mező, Gábor}
}

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