Cargando…

The organic ester O,O’-diethyl-(S,S)-ethylenediamine-N,N’-di-2-(3-cyclohexyl)propanoate dihydrochloride attenuates murine breast cancer growth and metastasis

Pharmacological treatment of cancer is mostly limited by drug-toxicity and resistance. It has been noticed that new organic ester ligand, O,O’-diethyl-(S,S)-ethylenediamine-N,N’-di-2-(3-cyclohexyl)propanoate dihydrochloride (named DE-EDCP) showed effective cytotoxic capacities against several human...

Descripción completa

Detalles Bibliográficos
Autores principales: Jurisevic, Milena, Arsenijevic, Aleksandar, Pantic, Jelena, Gajovic, Nevena, Milovanovic, Jelena, Milovanovic, Marija, Poljarevic, Jelena, Sabo, Tibor, Vojvodic, Danilo, Radosavljevic, Gordana D., Arsenijevic, Nebojsa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6021340/
https://www.ncbi.nlm.nih.gov/pubmed/29963272
http://dx.doi.org/10.18632/oncotarget.25610
_version_ 1783335448866717696
author Jurisevic, Milena
Arsenijevic, Aleksandar
Pantic, Jelena
Gajovic, Nevena
Milovanovic, Jelena
Milovanovic, Marija
Poljarevic, Jelena
Sabo, Tibor
Vojvodic, Danilo
Radosavljevic, Gordana D.
Arsenijevic, Nebojsa
author_facet Jurisevic, Milena
Arsenijevic, Aleksandar
Pantic, Jelena
Gajovic, Nevena
Milovanovic, Jelena
Milovanovic, Marija
Poljarevic, Jelena
Sabo, Tibor
Vojvodic, Danilo
Radosavljevic, Gordana D.
Arsenijevic, Nebojsa
author_sort Jurisevic, Milena
collection PubMed
description Pharmacological treatment of cancer is mostly limited by drug-toxicity and resistance. It has been noticed that new organic ester ligand, O,O’-diethyl-(S,S)-ethylenediamine-N,N’-di-2-(3-cyclohexyl)propanoate dihydrochloride (named DE-EDCP) showed effective cytotoxic capacities against several human and mouse cancer cell lines. However, its effects on tumor growth and metastasis are unexplored. The aim of present study was to examine the ability of DE-EDCP to inhibit 4T1 murine breast cancer growth and progression and to explore possible molecular mechanisms. DE-EDCP exhibited significant tumoricidal activity on human and murine breast cancer cell lines. Further, marked reduction of murine breast cancer growth and progression by DE-EDCP was shown. DE-EDCP exhibits fewer side-effects compared to cisplatin as a conventional chemotherapeutic. Results obtained from in vivo and in vitro experiments indicate that DE-EDCP induces apoptosis and inhibits proliferation of 4T1 cells. DE-EDCP increases percentage of 4T1 cells in late apoptosis, expression of pro-apoptotic Bax and caspase-3, while decreases expression of anti-apoptotic Bcl-2. DE-EDCP treatment increased the percentage of TUNEL-positive nuclei and reduced Ki-67 expression in breast cancer tissue. DE-EDCP decreased expression of cyclin D3 and Ki-67, increased expression of cyclin-dependent kinase inhibitors p16, p21 and p27 and arrested 4T1 cells in G0/G1 cell cycle phase. Expression of STAT3 and downstream regulated molecules, NANOG and SOX2, was reduced in 4T1 cells after DE-EDCP treatment. In conclusion, DE-EDCP impairs breast cancer growth and progression by triggering cancer cell death and inhibition of cancer cell proliferation. DE-EDCP might be of interest in the development of the new anticancer agent.
format Online
Article
Text
id pubmed-6021340
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Impact Journals LLC
record_format MEDLINE/PubMed
spelling pubmed-60213402018-06-30 The organic ester O,O’-diethyl-(S,S)-ethylenediamine-N,N’-di-2-(3-cyclohexyl)propanoate dihydrochloride attenuates murine breast cancer growth and metastasis Jurisevic, Milena Arsenijevic, Aleksandar Pantic, Jelena Gajovic, Nevena Milovanovic, Jelena Milovanovic, Marija Poljarevic, Jelena Sabo, Tibor Vojvodic, Danilo Radosavljevic, Gordana D. Arsenijevic, Nebojsa Oncotarget Research Paper Pharmacological treatment of cancer is mostly limited by drug-toxicity and resistance. It has been noticed that new organic ester ligand, O,O’-diethyl-(S,S)-ethylenediamine-N,N’-di-2-(3-cyclohexyl)propanoate dihydrochloride (named DE-EDCP) showed effective cytotoxic capacities against several human and mouse cancer cell lines. However, its effects on tumor growth and metastasis are unexplored. The aim of present study was to examine the ability of DE-EDCP to inhibit 4T1 murine breast cancer growth and progression and to explore possible molecular mechanisms. DE-EDCP exhibited significant tumoricidal activity on human and murine breast cancer cell lines. Further, marked reduction of murine breast cancer growth and progression by DE-EDCP was shown. DE-EDCP exhibits fewer side-effects compared to cisplatin as a conventional chemotherapeutic. Results obtained from in vivo and in vitro experiments indicate that DE-EDCP induces apoptosis and inhibits proliferation of 4T1 cells. DE-EDCP increases percentage of 4T1 cells in late apoptosis, expression of pro-apoptotic Bax and caspase-3, while decreases expression of anti-apoptotic Bcl-2. DE-EDCP treatment increased the percentage of TUNEL-positive nuclei and reduced Ki-67 expression in breast cancer tissue. DE-EDCP decreased expression of cyclin D3 and Ki-67, increased expression of cyclin-dependent kinase inhibitors p16, p21 and p27 and arrested 4T1 cells in G0/G1 cell cycle phase. Expression of STAT3 and downstream regulated molecules, NANOG and SOX2, was reduced in 4T1 cells after DE-EDCP treatment. In conclusion, DE-EDCP impairs breast cancer growth and progression by triggering cancer cell death and inhibition of cancer cell proliferation. DE-EDCP might be of interest in the development of the new anticancer agent. Impact Journals LLC 2018-06-15 /pmc/articles/PMC6021340/ /pubmed/29963272 http://dx.doi.org/10.18632/oncotarget.25610 Text en Copyright: © 2018 Jurisevic et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Jurisevic, Milena
Arsenijevic, Aleksandar
Pantic, Jelena
Gajovic, Nevena
Milovanovic, Jelena
Milovanovic, Marija
Poljarevic, Jelena
Sabo, Tibor
Vojvodic, Danilo
Radosavljevic, Gordana D.
Arsenijevic, Nebojsa
The organic ester O,O’-diethyl-(S,S)-ethylenediamine-N,N’-di-2-(3-cyclohexyl)propanoate dihydrochloride attenuates murine breast cancer growth and metastasis
title The organic ester O,O’-diethyl-(S,S)-ethylenediamine-N,N’-di-2-(3-cyclohexyl)propanoate dihydrochloride attenuates murine breast cancer growth and metastasis
title_full The organic ester O,O’-diethyl-(S,S)-ethylenediamine-N,N’-di-2-(3-cyclohexyl)propanoate dihydrochloride attenuates murine breast cancer growth and metastasis
title_fullStr The organic ester O,O’-diethyl-(S,S)-ethylenediamine-N,N’-di-2-(3-cyclohexyl)propanoate dihydrochloride attenuates murine breast cancer growth and metastasis
title_full_unstemmed The organic ester O,O’-diethyl-(S,S)-ethylenediamine-N,N’-di-2-(3-cyclohexyl)propanoate dihydrochloride attenuates murine breast cancer growth and metastasis
title_short The organic ester O,O’-diethyl-(S,S)-ethylenediamine-N,N’-di-2-(3-cyclohexyl)propanoate dihydrochloride attenuates murine breast cancer growth and metastasis
title_sort organic ester o,o’-diethyl-(s,s)-ethylenediamine-n,n’-di-2-(3-cyclohexyl)propanoate dihydrochloride attenuates murine breast cancer growth and metastasis
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6021340/
https://www.ncbi.nlm.nih.gov/pubmed/29963272
http://dx.doi.org/10.18632/oncotarget.25610
work_keys_str_mv AT jurisevicmilena theorganicesteroodiethylssethylenediaminenndi23cyclohexylpropanoatedihydrochlorideattenuatesmurinebreastcancergrowthandmetastasis
AT arsenijevicaleksandar theorganicesteroodiethylssethylenediaminenndi23cyclohexylpropanoatedihydrochlorideattenuatesmurinebreastcancergrowthandmetastasis
AT panticjelena theorganicesteroodiethylssethylenediaminenndi23cyclohexylpropanoatedihydrochlorideattenuatesmurinebreastcancergrowthandmetastasis
AT gajovicnevena theorganicesteroodiethylssethylenediaminenndi23cyclohexylpropanoatedihydrochlorideattenuatesmurinebreastcancergrowthandmetastasis
AT milovanovicjelena theorganicesteroodiethylssethylenediaminenndi23cyclohexylpropanoatedihydrochlorideattenuatesmurinebreastcancergrowthandmetastasis
AT milovanovicmarija theorganicesteroodiethylssethylenediaminenndi23cyclohexylpropanoatedihydrochlorideattenuatesmurinebreastcancergrowthandmetastasis
AT poljarevicjelena theorganicesteroodiethylssethylenediaminenndi23cyclohexylpropanoatedihydrochlorideattenuatesmurinebreastcancergrowthandmetastasis
AT sabotibor theorganicesteroodiethylssethylenediaminenndi23cyclohexylpropanoatedihydrochlorideattenuatesmurinebreastcancergrowthandmetastasis
AT vojvodicdanilo theorganicesteroodiethylssethylenediaminenndi23cyclohexylpropanoatedihydrochlorideattenuatesmurinebreastcancergrowthandmetastasis
AT radosavljevicgordanad theorganicesteroodiethylssethylenediaminenndi23cyclohexylpropanoatedihydrochlorideattenuatesmurinebreastcancergrowthandmetastasis
AT arsenijevicnebojsa theorganicesteroodiethylssethylenediaminenndi23cyclohexylpropanoatedihydrochlorideattenuatesmurinebreastcancergrowthandmetastasis
AT jurisevicmilena organicesteroodiethylssethylenediaminenndi23cyclohexylpropanoatedihydrochlorideattenuatesmurinebreastcancergrowthandmetastasis
AT arsenijevicaleksandar organicesteroodiethylssethylenediaminenndi23cyclohexylpropanoatedihydrochlorideattenuatesmurinebreastcancergrowthandmetastasis
AT panticjelena organicesteroodiethylssethylenediaminenndi23cyclohexylpropanoatedihydrochlorideattenuatesmurinebreastcancergrowthandmetastasis
AT gajovicnevena organicesteroodiethylssethylenediaminenndi23cyclohexylpropanoatedihydrochlorideattenuatesmurinebreastcancergrowthandmetastasis
AT milovanovicjelena organicesteroodiethylssethylenediaminenndi23cyclohexylpropanoatedihydrochlorideattenuatesmurinebreastcancergrowthandmetastasis
AT milovanovicmarija organicesteroodiethylssethylenediaminenndi23cyclohexylpropanoatedihydrochlorideattenuatesmurinebreastcancergrowthandmetastasis
AT poljarevicjelena organicesteroodiethylssethylenediaminenndi23cyclohexylpropanoatedihydrochlorideattenuatesmurinebreastcancergrowthandmetastasis
AT sabotibor organicesteroodiethylssethylenediaminenndi23cyclohexylpropanoatedihydrochlorideattenuatesmurinebreastcancergrowthandmetastasis
AT vojvodicdanilo organicesteroodiethylssethylenediaminenndi23cyclohexylpropanoatedihydrochlorideattenuatesmurinebreastcancergrowthandmetastasis
AT radosavljevicgordanad organicesteroodiethylssethylenediaminenndi23cyclohexylpropanoatedihydrochlorideattenuatesmurinebreastcancergrowthandmetastasis
AT arsenijevicnebojsa organicesteroodiethylssethylenediaminenndi23cyclohexylpropanoatedihydrochlorideattenuatesmurinebreastcancergrowthandmetastasis