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Non-substituted N-heteroaromatic selenosemicarbazone metal complexes induce apoptosis in cancer cells via activation of mitochondrial pathway

Authorized Users Only
2011
Authors
Srdić-Rajić, Tatjana
Zec, Manja M.
Todorović, Tamara
Anđelković, Katarina
Radulović, Siniša
Article (Published version)
Metadata
Show full item record
Abstract
We previously published the synthesis, characterization and cytotoxic effect of the novel Zn(II), Ni(II), and Cd(II) complexes with 2-formylpyridine selenosemicarbazone. Here we further investigate the mechanism of their antiproliferative activity against several cancer and vascular endothelial cell lines and compared it to the activity of the ligand itself, corresponding salts and, as a referent compound, cisplatin. Investigated complexes induced apoptosis in a time- and dose-dependent manner as well as changes in a cell cycle distribution. Caspase-3 activation in HeLa cells, MDA-MB-361 and vascular endothelial cells EA.hy 926 cells by ligand alone, as well as Zn(II), Ni(II), and Cd(II) complexes was preceded by the activation of the p53 tumor-suppressor gene family protein p73. In addition to activation of p73, these compounds also trigger cytochrome C release by upregulation of Bax expression. The release of cytochrome C has been linked to loss of mitochondrial membrane potential. H...owever, our data indicated that the increased phosphorylation of ERK could be also one of the mechanism involved in the Zn(II), and Cd(II) complexes- induction of apoptosis. Selenosemicarbazone complexes with Cd(II) and Ni(II), possess dual ability to induce apoptosis as well as necrosis, and might present an added advantage for inducing cell death in a diverse array of malignant cells. Taken together, our findings could indicate potential role of these complexes as activator of cross-talk between different signaling pathways that leads to cell death, and thus making the complex intriguing field for further scientific, and maybe clinical investigations.

Keywords:
Zn(II), Ni(II), and Cd(II) complexes / Selenosemicarbazone / Antiproliferative activity / Apoptosis
Source:
European Journal of Medicinal Chemistry, 2011, 46, 9, 3734-3747
Publisher:
  • Elsevier France-Editions Scientifiques Medicales Elsevier, Issy-Les-Moulineaux
Funding / projects:
  • Pharmacodynamic and pharmacogenomic research of new drugs in the treatment of solid tumors (RS-41026)
  • Interactions of natural products, their derivatives and coordination compounds with proteins and nucleic acids (RS-172055)

DOI: 10.1016/j.ejmech.2011.05.039

ISSN: 0223-5234

PubMed: 21641698

WoS: 000295237400021

Scopus: 2-s2.0-80052960393
[ Google Scholar ]
36
29
URI
http://rimi.imi.bg.ac.rs/handle/123456789/334
Collections
  • Radovi istraživača / Researchers' publications
Institution/Community
Institut za medicinska istraživanja
TY  - JOUR
AU  - Srdić-Rajić, Tatjana
AU  - Zec, Manja M.
AU  - Todorović, Tamara
AU  - Anđelković, Katarina
AU  - Radulović, Siniša
PY  - 2011
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/334
AB  - We previously published the synthesis, characterization and cytotoxic effect of the novel Zn(II), Ni(II), and Cd(II) complexes with 2-formylpyridine selenosemicarbazone. Here we further investigate the mechanism of their antiproliferative activity against several cancer and vascular endothelial cell lines and compared it to the activity of the ligand itself, corresponding salts and, as a referent compound, cisplatin. Investigated complexes induced apoptosis in a time- and dose-dependent manner as well as changes in a cell cycle distribution. Caspase-3 activation in HeLa cells, MDA-MB-361 and vascular endothelial cells EA.hy 926 cells by ligand alone, as well as Zn(II), Ni(II), and Cd(II) complexes was preceded by the activation of the p53 tumor-suppressor gene family protein p73. In addition to activation of p73, these compounds also trigger cytochrome C release by upregulation of Bax expression. The release of cytochrome C has been linked to loss of mitochondrial membrane potential. However, our data indicated that the increased phosphorylation of ERK could be also one of the mechanism involved in the Zn(II), and Cd(II) complexes- induction of apoptosis. Selenosemicarbazone complexes with Cd(II) and Ni(II), possess dual ability to induce apoptosis as well as necrosis, and might present an added advantage for inducing cell death in a diverse array of malignant cells. Taken together, our findings could indicate potential role of these complexes as activator of cross-talk between different signaling pathways that leads to cell death, and thus making the complex intriguing field for further scientific, and maybe clinical investigations.
PB  - Elsevier France-Editions Scientifiques Medicales Elsevier, Issy-Les-Moulineaux
T2  - European Journal of Medicinal Chemistry
T1  - Non-substituted N-heteroaromatic selenosemicarbazone metal complexes induce apoptosis in cancer cells via activation of mitochondrial pathway
EP  - 3747
IS  - 9
SP  - 3734
VL  - 46
DO  - 10.1016/j.ejmech.2011.05.039
UR  - conv_2526
ER  - 
@article{
author = "Srdić-Rajić, Tatjana and Zec, Manja M. and Todorović, Tamara and Anđelković, Katarina and Radulović, Siniša",
year = "2011",
abstract = "We previously published the synthesis, characterization and cytotoxic effect of the novel Zn(II), Ni(II), and Cd(II) complexes with 2-formylpyridine selenosemicarbazone. Here we further investigate the mechanism of their antiproliferative activity against several cancer and vascular endothelial cell lines and compared it to the activity of the ligand itself, corresponding salts and, as a referent compound, cisplatin. Investigated complexes induced apoptosis in a time- and dose-dependent manner as well as changes in a cell cycle distribution. Caspase-3 activation in HeLa cells, MDA-MB-361 and vascular endothelial cells EA.hy 926 cells by ligand alone, as well as Zn(II), Ni(II), and Cd(II) complexes was preceded by the activation of the p53 tumor-suppressor gene family protein p73. In addition to activation of p73, these compounds also trigger cytochrome C release by upregulation of Bax expression. The release of cytochrome C has been linked to loss of mitochondrial membrane potential. However, our data indicated that the increased phosphorylation of ERK could be also one of the mechanism involved in the Zn(II), and Cd(II) complexes- induction of apoptosis. Selenosemicarbazone complexes with Cd(II) and Ni(II), possess dual ability to induce apoptosis as well as necrosis, and might present an added advantage for inducing cell death in a diverse array of malignant cells. Taken together, our findings could indicate potential role of these complexes as activator of cross-talk between different signaling pathways that leads to cell death, and thus making the complex intriguing field for further scientific, and maybe clinical investigations.",
publisher = "Elsevier France-Editions Scientifiques Medicales Elsevier, Issy-Les-Moulineaux",
journal = "European Journal of Medicinal Chemistry",
title = "Non-substituted N-heteroaromatic selenosemicarbazone metal complexes induce apoptosis in cancer cells via activation of mitochondrial pathway",
pages = "3747-3734",
number = "9",
volume = "46",
doi = "10.1016/j.ejmech.2011.05.039",
url = "conv_2526"
}
Srdić-Rajić, T., Zec, M. M., Todorović, T., Anđelković, K.,& Radulović, S.. (2011). Non-substituted N-heteroaromatic selenosemicarbazone metal complexes induce apoptosis in cancer cells via activation of mitochondrial pathway. in European Journal of Medicinal Chemistry
Elsevier France-Editions Scientifiques Medicales Elsevier, Issy-Les-Moulineaux., 46(9), 3734-3747.
https://doi.org/10.1016/j.ejmech.2011.05.039
conv_2526
Srdić-Rajić T, Zec MM, Todorović T, Anđelković K, Radulović S. Non-substituted N-heteroaromatic selenosemicarbazone metal complexes induce apoptosis in cancer cells via activation of mitochondrial pathway. in European Journal of Medicinal Chemistry. 2011;46(9):3734-3747.
doi:10.1016/j.ejmech.2011.05.039
conv_2526 .
Srdić-Rajić, Tatjana, Zec, Manja M., Todorović, Tamara, Anđelković, Katarina, Radulović, Siniša, "Non-substituted N-heteroaromatic selenosemicarbazone metal complexes induce apoptosis in cancer cells via activation of mitochondrial pathway" in European Journal of Medicinal Chemistry, 46, no. 9 (2011):3734-3747,
https://doi.org/10.1016/j.ejmech.2011.05.039 .,
conv_2526 .

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