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
Аутори
Filipović, NenadBjelogrlić, Snežana
Marković, Sanja
Araškov, Jovana
Muller, Christian
Todorović, Tamara
Конференцијски прилог (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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.
Кључне речи:
Cd complex / hydrazones / antitumor activity / apoptosisИзвор:
IV annual COST ACTION CA15135 meeting Paul Ehrlich Euro-PhD Network & MuTaLig COST Action meeting, Catanzaro, Italy, June 13-15, 2019, 2019Издавач:
- Università “Magna Græcia” di Catanzaro, Italy
Колекције
Институција/група
Hemijski fakultet / Faculty of ChemistryTY - CONF AU - Filipović, Nenad AU - Bjelogrlić, Snežana AU - Marković, Sanja AU - Araškov, Jovana AU - Muller, Christian AU - Todorović, Tamara PY - 2019 UR - http://cherry.chem.bg.ac.rs/handle/123456789/6009 AB - 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. PB - Università “Magna Græcia” di Catanzaro, Italy C3 - IV annual COST ACTION CA15135 meeting Paul Ehrlich Euro-PhD Network & MuTaLig COST Action meeting, Catanzaro, Italy, June 13-15, 2019 T1 - 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 UR - https://hdl.handle.net/21.15107/rcub_cherry_6009 ER -
@conference{ author = "Filipović, Nenad and Bjelogrlić, Snežana and Marković, Sanja and Araškov, Jovana and Muller, Christian and Todorović, Tamara", year = "2019", 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.", publisher = "Università “Magna Græcia” di Catanzaro, Italy", journal = "IV annual COST ACTION CA15135 meeting Paul Ehrlich Euro-PhD Network & MuTaLig COST Action meeting, Catanzaro, Italy, June 13-15, 2019", 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", url = "https://hdl.handle.net/21.15107/rcub_cherry_6009" }
Filipović, N., Bjelogrlić, S., Marković, S., Araškov, J., Muller, C.,& Todorović, T.. (2019). 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. in IV annual COST ACTION CA15135 meeting Paul Ehrlich Euro-PhD Network & MuTaLig COST Action meeting, Catanzaro, Italy, June 13-15, 2019 Università “Magna Græcia” di Catanzaro, Italy.. https://hdl.handle.net/21.15107/rcub_cherry_6009
Filipović N, Bjelogrlić S, Marković S, Araškov J, Muller C, Todorović T. 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. in IV annual COST ACTION CA15135 meeting Paul Ehrlich Euro-PhD Network & MuTaLig COST Action meeting, Catanzaro, Italy, June 13-15, 2019. 2019;. https://hdl.handle.net/21.15107/rcub_cherry_6009 .
Filipović, Nenad, Bjelogrlić, Snežana, Marković, Sanja, Araškov, Jovana, Muller, Christian, Todorović, Tamara, "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" in IV annual COST ACTION CA15135 meeting Paul Ehrlich Euro-PhD Network & MuTaLig COST Action meeting, Catanzaro, Italy, June 13-15, 2019 (2019), https://hdl.handle.net/21.15107/rcub_cherry_6009 .