Novel Selenosemicarbazone Metal Complexes Exert Anti-tumor Effect via Alternative, Caspase-independent Necroptotic Cell Death
Нема приказа
Аутори
Zec, Manja M.Srdić-Rajić, Tatjana
Krivokuca, Ana
Janković, Radmila
Todorović, Tamara
Anđelković, Katarina
Radulović, Siniša
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
The synthesis and chemical characterization of the novel 2,6-diacetylpyridine-bis(selenosemicarbazone) metal complexes of Zn(II), Cd(II) and Ni(II) were published previously. Here we report first evidence on anti-proliferative activity of the complexes and molecular patterns that underlie it. The complexes and the corresponding ligand are shown to be cytotoxic on the panel of nine, malignant and non-malignant cell lines, with the exception of Ni(II) complex that did not achieve IC50 value on any of the cell lines tested. Further experiments on the selected cell lines including A 549, MRC-5, EA.hy 926 and HeLa, have shown that the complexes posses unambiguous property of inducing necrosis in the cells treated for 6 hours, with the ligand and Zn(II) complex being the most active on all cell lines. On the contrary, only small portion of early apoptotic events was detected, under the same experimental condition. This was in complete concordance with the results obtained from Western blot a...nalysis of the treated cells that showed no or slight increase of the protein amounts of two crucial apoptotic mediators: Cytochrome C and Caspase III. We propose the model, under which tested complexes induce necroptosis in treated cells, a recently described type of cell death with necrotic morphological features and acting via caspase independent pathway, and without elevated amounts of intracellular ROS. Endothelial EA.hy 926 cells have proven to be extremely sensitive on the necrosis-inducing effect of the complexes, which could indicate potential anti-angiogenic effect of the novel complexes that is to be investigated.
Кључне речи:
A 549 / EA.hy 926 / metal complexes / necroptosis / ROS / selenosemicarbazone / zinc (II) complexИзвор:
Medicinal Chemistry, 2014, 10, 8, 759-771Издавач:
- Bentham Science Publ Ltd, Sharjah
Финансирање / пројекти:
- Фармакодинамска и фармакогеномска испитивања новијих лекова у лечењу солидних тумора (RS-41026)
- Интеракције природних производа, њихових деривата и комплексних једињења са протеинима и нуклеинским киселинама (RS-172055)
DOI: 10.2174/1573406410666140327122009
ISSN: 1573-4064
PubMed: 24678785
WoS: 000344525700002
Scopus: 2-s2.0-84908680415
Институција/група
Institut za medicinska istraživanjaTY - JOUR AU - Zec, Manja M. AU - Srdić-Rajić, Tatjana AU - Krivokuca, Ana AU - Janković, Radmila AU - Todorović, Tamara AU - Anđelković, Katarina AU - Radulović, Siniša PY - 2014 UR - http://rimi.imi.bg.ac.rs/handle/123456789/561 AB - The synthesis and chemical characterization of the novel 2,6-diacetylpyridine-bis(selenosemicarbazone) metal complexes of Zn(II), Cd(II) and Ni(II) were published previously. Here we report first evidence on anti-proliferative activity of the complexes and molecular patterns that underlie it. The complexes and the corresponding ligand are shown to be cytotoxic on the panel of nine, malignant and non-malignant cell lines, with the exception of Ni(II) complex that did not achieve IC50 value on any of the cell lines tested. Further experiments on the selected cell lines including A 549, MRC-5, EA.hy 926 and HeLa, have shown that the complexes posses unambiguous property of inducing necrosis in the cells treated for 6 hours, with the ligand and Zn(II) complex being the most active on all cell lines. On the contrary, only small portion of early apoptotic events was detected, under the same experimental condition. This was in complete concordance with the results obtained from Western blot analysis of the treated cells that showed no or slight increase of the protein amounts of two crucial apoptotic mediators: Cytochrome C and Caspase III. We propose the model, under which tested complexes induce necroptosis in treated cells, a recently described type of cell death with necrotic morphological features and acting via caspase independent pathway, and without elevated amounts of intracellular ROS. Endothelial EA.hy 926 cells have proven to be extremely sensitive on the necrosis-inducing effect of the complexes, which could indicate potential anti-angiogenic effect of the novel complexes that is to be investigated. PB - Bentham Science Publ Ltd, Sharjah T2 - Medicinal Chemistry T1 - Novel Selenosemicarbazone Metal Complexes Exert Anti-tumor Effect via Alternative, Caspase-independent Necroptotic Cell Death EP - 771 IS - 8 SP - 759 VL - 10 DO - 10.2174/1573406410666140327122009 ER -
@article{ author = "Zec, Manja M. and Srdić-Rajić, Tatjana and Krivokuca, Ana and Janković, Radmila and Todorović, Tamara and Anđelković, Katarina and Radulović, Siniša", year = "2014", abstract = "The synthesis and chemical characterization of the novel 2,6-diacetylpyridine-bis(selenosemicarbazone) metal complexes of Zn(II), Cd(II) and Ni(II) were published previously. Here we report first evidence on anti-proliferative activity of the complexes and molecular patterns that underlie it. The complexes and the corresponding ligand are shown to be cytotoxic on the panel of nine, malignant and non-malignant cell lines, with the exception of Ni(II) complex that did not achieve IC50 value on any of the cell lines tested. Further experiments on the selected cell lines including A 549, MRC-5, EA.hy 926 and HeLa, have shown that the complexes posses unambiguous property of inducing necrosis in the cells treated for 6 hours, with the ligand and Zn(II) complex being the most active on all cell lines. On the contrary, only small portion of early apoptotic events was detected, under the same experimental condition. This was in complete concordance with the results obtained from Western blot analysis of the treated cells that showed no or slight increase of the protein amounts of two crucial apoptotic mediators: Cytochrome C and Caspase III. We propose the model, under which tested complexes induce necroptosis in treated cells, a recently described type of cell death with necrotic morphological features and acting via caspase independent pathway, and without elevated amounts of intracellular ROS. Endothelial EA.hy 926 cells have proven to be extremely sensitive on the necrosis-inducing effect of the complexes, which could indicate potential anti-angiogenic effect of the novel complexes that is to be investigated.", publisher = "Bentham Science Publ Ltd, Sharjah", journal = "Medicinal Chemistry", title = "Novel Selenosemicarbazone Metal Complexes Exert Anti-tumor Effect via Alternative, Caspase-independent Necroptotic Cell Death", pages = "771-759", number = "8", volume = "10", doi = "10.2174/1573406410666140327122009" }
Zec, M. M., Srdić-Rajić, T., Krivokuca, A., Janković, R., Todorović, T., Anđelković, K.,& Radulović, S.. (2014). Novel Selenosemicarbazone Metal Complexes Exert Anti-tumor Effect via Alternative, Caspase-independent Necroptotic Cell Death. in Medicinal Chemistry Bentham Science Publ Ltd, Sharjah., 10(8), 759-771. https://doi.org/10.2174/1573406410666140327122009
Zec MM, Srdić-Rajić T, Krivokuca A, Janković R, Todorović T, Anđelković K, Radulović S. Novel Selenosemicarbazone Metal Complexes Exert Anti-tumor Effect via Alternative, Caspase-independent Necroptotic Cell Death. in Medicinal Chemistry. 2014;10(8):759-771. doi:10.2174/1573406410666140327122009 .
Zec, Manja M., Srdić-Rajić, Tatjana, Krivokuca, Ana, Janković, Radmila, Todorović, Tamara, Anđelković, Katarina, Radulović, Siniša, "Novel Selenosemicarbazone Metal Complexes Exert Anti-tumor Effect via Alternative, Caspase-independent Necroptotic Cell Death" in Medicinal Chemistry, 10, no. 8 (2014):759-771, https://doi.org/10.2174/1573406410666140327122009 . .