@ARTICLE{Bjelogrlic201945,
author={Bjelogrlić, S. and Todorović, T.R. and Cvijetić, I. and Rodić, M.V. and Vujčić, M. and Marković, S. and Araškov, J. and Janović, B. and Emhemmed, F. and Muller, C.D. and Filipović, N.R.},
title={A novel binuclear hydrazone-based Cd(II) complex is a strong pro-apoptotic inducer with significant activity against 2D and 3D pancreatic cancer stem cells},
journal={Journal of Inorganic Biochemistry},
year={2019},
volume={190},
pages={45-66},
doi={10.1016/j.jinorgbio.2018.10.002},
url={https://www.scopus.com/inward/record.uri?eid=2-s2.0-85055090720&doi=10.1016%2fj.jinorgbio.2018.10.002&partnerID=40&md5=dd6d19729559fb60333c6f81e7ab9ca3},
abstract={A novel binuclear Cd complex (1) with hydrazone-based ligand was prepared and characterized by spectroscopy and single crystal X-ray diffraction techniques. Complex 1 reveals a strong pro-apoptotic activity in both human, mammary adenocarcinoma cells (MCF-7) and pancreatic AsPC-1 cancer stem cells (CSCs). While apoptosis undergoes mostly caspase-independent, 1 stimulates the activation of intrinsic pathway with noteworthy down regulation of caspase-8 activity in respect to non-treated controls. Distribution of cells over mitotic division indicates that 1 caused DNA damage in both cell lines, which is confirmed in DNA interaction studies. Compared to 1, cisplatin (CDDP) does not achieve cell death in 2D cultured AsPC-1 cells, while induces different pattern of cell cycle changes and caspase activation in 2D cultured MCF-7 cells, implying that these two compounds do not share similar mechanism of action. Additionally, 1 acts as a powerful inducer of mitochondrial superoxide production with dissipated trans-membrane potential in the majority of the treated cells already after 6 h of incubation. On 3D tumors, 1 displays a superior activity against CSC model, and at 100 μM induces disintegration of spheroids within 2 days of incubation. Fluorescence spectroscopy, along with molecular docking show that compound 1 binds to the minor groove of DNA. Compound 1 binds to the human serum albumin (HSA) showing that the HSA can effectively transport and store 1 in the human body. Thus, our current study strongly supports further investigations on antitumor activity of 1 as a drug candidate for the treatment of highly resistant pancreatic cancer. © 2018 Elsevier Inc.},
author_keywords={Apoptosis;  Cancer stem cells;  Cd(II) complex;  DNA interactions;  HSA interactions;  Hydrazones},
publisher={Elsevier Inc.},
issn={01620134},
coden={JIBID},
abbrev_source_title={J. Inorg. Biochem.},
document_type={Article},
source={Scopus},
}

{"_id":"PBmsqGJhg56kFg48g","bibbaseid":"bjelogrli-todorovi-cvijeti-rodi-vuji-markovi-arakov-janovi-etal-anovelbinuclearhydrazonebasedcdiicomplexisastrongproapoptoticinducerwithsignificantactivityagainst2dand3dpancreaticcancerstemcells-2019","author_short":["Bjelogrlić, S.","Todorović, T.","Cvijetić, I.","Rodić, M.","Vujčić, M.","Marković, S.","Araškov, J.","Janović, B.","Emhemmed, F.","Muller, C.","Filipović, N."],"bibdata":{"bibtype":"article","type":"article","author":[{"propositions":[],"lastnames":["Bjelogrlić"],"firstnames":["S."],"suffixes":[]},{"propositions":[],"lastnames":["Todorović"],"firstnames":["T.R."],"suffixes":[]},{"propositions":[],"lastnames":["Cvijetić"],"firstnames":["I."],"suffixes":[]},{"propositions":[],"lastnames":["Rodić"],"firstnames":["M.V."],"suffixes":[]},{"propositions":[],"lastnames":["Vujčić"],"firstnames":["M."],"suffixes":[]},{"propositions":[],"lastnames":["Marković"],"firstnames":["S."],"suffixes":[]},{"propositions":[],"lastnames":["Araškov"],"firstnames":["J."],"suffixes":[]},{"propositions":[],"lastnames":["Janović"],"firstnames":["B."],"suffixes":[]},{"propositions":[],"lastnames":["Emhemmed"],"firstnames":["F."],"suffixes":[]},{"propositions":[],"lastnames":["Muller"],"firstnames":["C.D."],"suffixes":[]},{"propositions":[],"lastnames":["Filipović"],"firstnames":["N.R."],"suffixes":[]}],"title":"A novel binuclear hydrazone-based Cd(II) complex is a strong pro-apoptotic inducer with significant activity against 2D and 3D pancreatic cancer stem cells","journal":"Journal of Inorganic Biochemistry","year":"2019","volume":"190","pages":"45-66","doi":"10.1016/j.jinorgbio.2018.10.002","url":"https://www.scopus.com/inward/record.uri?eid=2-s2.0-85055090720&doi=10.1016%2fj.jinorgbio.2018.10.002&partnerID=40&md5=dd6d19729559fb60333c6f81e7ab9ca3","abstract":"A novel binuclear Cd complex (1) with hydrazone-based ligand was prepared and characterized by spectroscopy and single crystal X-ray diffraction techniques. Complex 1 reveals a strong pro-apoptotic activity in both human, mammary adenocarcinoma cells (MCF-7) and pancreatic AsPC-1 cancer stem cells (CSCs). While apoptosis undergoes mostly caspase-independent, 1 stimulates the activation of intrinsic pathway with noteworthy down regulation of caspase-8 activity in respect to non-treated controls. Distribution of cells over mitotic division indicates that 1 caused DNA damage in both cell lines, which is confirmed in DNA interaction studies. Compared to 1, cisplatin (CDDP) does not achieve cell death in 2D cultured AsPC-1 cells, while induces different pattern of cell cycle changes and caspase activation in 2D cultured MCF-7 cells, implying that these two compounds do not share similar mechanism of action. Additionally, 1 acts as a powerful inducer of mitochondrial superoxide production with dissipated trans-membrane potential in the majority of the treated cells already after 6 h of incubation. On 3D tumors, 1 displays a superior activity against CSC model, and at 100 μM induces disintegration of spheroids within 2 days of incubation. Fluorescence spectroscopy, along with molecular docking show that compound 1 binds to the minor groove of DNA. Compound 1 binds to the human serum albumin (HSA) showing that the HSA can effectively transport and store 1 in the human body. Thus, our current study strongly supports further investigations on antitumor activity of 1 as a drug candidate for the treatment of highly resistant pancreatic cancer. © 2018 Elsevier Inc.","author_keywords":"Apoptosis; Cancer stem cells; Cd(II) complex; DNA interactions; HSA interactions; Hydrazones","publisher":"Elsevier Inc.","issn":"01620134","coden":"JIBID","abbrev_source_title":"J. Inorg. Biochem.","document_type":"Article","source":"Scopus","bibtex":"@ARTICLE{Bjelogrlic201945,\nauthor={Bjelogrlić, S. and Todorović, T.R. and Cvijetić, I. and Rodić, M.V. and Vujčić, M. and Marković, S. and Araškov, J. and Janović, B. and Emhemmed, F. and Muller, C.D. and Filipović, N.R.},\ntitle={A novel binuclear hydrazone-based Cd(II) complex is a strong pro-apoptotic inducer with significant activity against 2D and 3D pancreatic cancer stem cells},\njournal={Journal of Inorganic Biochemistry},\nyear={2019},\nvolume={190},\npages={45-66},\ndoi={10.1016/j.jinorgbio.2018.10.002},\nurl={https://www.scopus.com/inward/record.uri?eid=2-s2.0-85055090720&doi=10.1016%2fj.jinorgbio.2018.10.002&partnerID=40&md5=dd6d19729559fb60333c6f81e7ab9ca3},\nabstract={A novel binuclear Cd complex (1) with hydrazone-based ligand was prepared and characterized by spectroscopy and single crystal X-ray diffraction techniques. Complex 1 reveals a strong pro-apoptotic activity in both human, mammary adenocarcinoma cells (MCF-7) and pancreatic AsPC-1 cancer stem cells (CSCs). While apoptosis undergoes mostly caspase-independent, 1 stimulates the activation of intrinsic pathway with noteworthy down regulation of caspase-8 activity in respect to non-treated controls. Distribution of cells over mitotic division indicates that 1 caused DNA damage in both cell lines, which is confirmed in DNA interaction studies. Compared to 1, cisplatin (CDDP) does not achieve cell death in 2D cultured AsPC-1 cells, while induces different pattern of cell cycle changes and caspase activation in 2D cultured MCF-7 cells, implying that these two compounds do not share similar mechanism of action. Additionally, 1 acts as a powerful inducer of mitochondrial superoxide production with dissipated trans-membrane potential in the majority of the treated cells already after 6 h of incubation. On 3D tumors, 1 displays a superior activity against CSC model, and at 100 μM induces disintegration of spheroids within 2 days of incubation. Fluorescence spectroscopy, along with molecular docking show that compound 1 binds to the minor groove of DNA. Compound 1 binds to the human serum albumin (HSA) showing that the HSA can effectively transport and store 1 in the human body. Thus, our current study strongly supports further investigations on antitumor activity of 1 as a drug candidate for the treatment of highly resistant pancreatic cancer. © 2018 Elsevier Inc.},\nauthor_keywords={Apoptosis; Cancer stem cells; Cd(II) complex; DNA interactions; HSA interactions; Hydrazones},\npublisher={Elsevier Inc.},\nissn={01620134},\ncoden={JIBID},\nabbrev_source_title={J. Inorg. Biochem.},\ndocument_type={Article},\nsource={Scopus},\n}\n\n","author_short":["Bjelogrlić, S.","Todorović, T.","Cvijetić, I.","Rodić, M.","Vujčić, M.","Marković, S.","Araškov, J.","Janović, B.","Emhemmed, F.","Muller, C.","Filipović, N."],"key":"Bjelogrlic201945","id":"Bjelogrlic201945","bibbaseid":"bjelogrli-todorovi-cvijeti-rodi-vuji-markovi-arakov-janovi-etal-anovelbinuclearhydrazonebasedcdiicomplexisastrongproapoptoticinducerwithsignificantactivityagainst2dand3dpancreaticcancerstemcells-2019","role":"author","urls":{"Paper":"https://www.scopus.com/inward/record.uri?eid=2-s2.0-85055090720&doi=10.1016%2fj.jinorgbio.2018.10.002&partnerID=40&md5=dd6d19729559fb60333c6f81e7ab9ca3"},"metadata":{"authorlinks":{}},"html":""},"bibtype":"article","biburl":"https://bibbase.org/network/files/3eEoTjibm7NHMv3Kj","dataSources":["NGkBwxQj7ESoiXTGz","Loz77B8tHQmYfRuYS","bSTZkZXREQFfAcBer","jneiCoXcWp9AqdscH","2bjxpE5TXzTKpwpod"],"keywords":[],"search_terms":["novel","binuclear","hydrazone","based","complex","strong","pro","apoptotic","inducer","significant","activity","against","pancreatic","cancer","stem","cells","bjelogrlić","todorović","cvijetić","rodić","vujčić","marković","araškov","janović","emhemmed","muller","filipović"],"title":"A novel binuclear hydrazone-based Cd(II) complex is a strong pro-apoptotic inducer with significant activity against 2D and 3D pancreatic cancer stem cells","year":2019}