Cargando…
Improved in vivo antitumor effect of a daunorubicin - GnRH-III bioconjugate modified by apoptosis inducing agent butyric acid on colorectal carcinoma bearing mice
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 su...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4919375/ https://www.ncbi.nlm.nih.gov/pubmed/27146514 http://dx.doi.org/10.1007/s10637-016-0354-7 |
_version_ | 1782439240108343296 |
---|---|
author | Kapuvári, Bence Hegedüs, Rózsa Schulcz, Ákos Manea, Marilena Tóvári, József Gacs, Alexandra Vincze, Borbála Mező, Gábor |
author_facet | Kapuvári, Bence Hegedüs, Rózsa Schulcz, Ákos Manea, Marilena Tóvári, József Gacs, Alexandra Vincze, Borbála Mező, Gábor |
author_sort | Kapuvári, Bence |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4919375 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-49193752016-07-07 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 Invest New Drugs Preclinical Studies 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. Springer US 2016-05-05 2016 /pmc/articles/PMC4919375/ /pubmed/27146514 http://dx.doi.org/10.1007/s10637-016-0354-7 Text en © The Author(s) 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Preclinical Studies 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 |
title | Improved in vivo antitumor effect of a daunorubicin - GnRH-III bioconjugate modified by apoptosis inducing agent butyric acid on colorectal carcinoma bearing mice |
title_full | Improved in vivo antitumor effect of a daunorubicin - GnRH-III bioconjugate modified by apoptosis inducing agent butyric acid on colorectal carcinoma bearing mice |
title_fullStr | Improved in vivo antitumor effect of a daunorubicin - GnRH-III bioconjugate modified by apoptosis inducing agent butyric acid on colorectal carcinoma bearing mice |
title_full_unstemmed | Improved in vivo antitumor effect of a daunorubicin - GnRH-III bioconjugate modified by apoptosis inducing agent butyric acid on colorectal carcinoma bearing mice |
title_short | Improved in vivo antitumor effect of a daunorubicin - GnRH-III bioconjugate modified by apoptosis inducing agent butyric acid on colorectal carcinoma bearing mice |
title_sort | improved in vivo antitumor effect of a daunorubicin - gnrh-iii bioconjugate modified by apoptosis inducing agent butyric acid on colorectal carcinoma bearing mice |
topic | Preclinical Studies |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4919375/ https://www.ncbi.nlm.nih.gov/pubmed/27146514 http://dx.doi.org/10.1007/s10637-016-0354-7 |
work_keys_str_mv | AT kapuvaribence improvedinvivoantitumoreffectofadaunorubicingnrhiiibioconjugatemodifiedbyapoptosisinducingagentbutyricacidoncolorectalcarcinomabearingmice AT hegedusrozsa improvedinvivoantitumoreffectofadaunorubicingnrhiiibioconjugatemodifiedbyapoptosisinducingagentbutyricacidoncolorectalcarcinomabearingmice AT schulczakos improvedinvivoantitumoreffectofadaunorubicingnrhiiibioconjugatemodifiedbyapoptosisinducingagentbutyricacidoncolorectalcarcinomabearingmice AT maneamarilena improvedinvivoantitumoreffectofadaunorubicingnrhiiibioconjugatemodifiedbyapoptosisinducingagentbutyricacidoncolorectalcarcinomabearingmice AT tovarijozsef improvedinvivoantitumoreffectofadaunorubicingnrhiiibioconjugatemodifiedbyapoptosisinducingagentbutyricacidoncolorectalcarcinomabearingmice AT gacsalexandra improvedinvivoantitumoreffectofadaunorubicingnrhiiibioconjugatemodifiedbyapoptosisinducingagentbutyricacidoncolorectalcarcinomabearingmice AT vinczeborbala improvedinvivoantitumoreffectofadaunorubicingnrhiiibioconjugatemodifiedbyapoptosisinducingagentbutyricacidoncolorectalcarcinomabearingmice AT mezogabor improvedinvivoantitumoreffectofadaunorubicingnrhiiibioconjugatemodifiedbyapoptosisinducingagentbutyricacidoncolorectalcarcinomabearingmice |