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

Bjelogrlić, Snežana K.; Todorović, Tamara; Cvijetić, Ilija; Rodić, Marko; Vujčić, Miroslava; Marković, Sanja B.; Araškov, Jovana; Janović, Barbara; Emhemmed, Fatihi; Muller, Christian D.; Filipović, Nenad R.

doi:10.1016/j.jinorgbio.2018.10.002

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 wi...

Keywords:

Apoptosis / Cancer stem cells / Cd(II) complex / DNA interactions / HSA interactions / Hydrazones

Source:
Journal of Inorganic Biochemistry, 2019, 190, 45-66

Funding / projects:

Interactions of natural products, their derivatives and coordination compounds with proteins and nucleic acids (RS-172055)

Note:

This is the peer-reviewed version of the article: Bjelogrlić, S., Todorović, T.R., Cvijetić, I., Rodić, M.V., Vujčić, M., Marković, S., Araškov, J., Janović, B., Emhemmed, F., Muller, C.D., Filipović, N.R., 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. Journal of Inorganic Biochemistry 190, 45–66. https://doi.org/10.1016/j.jinorgbio.2018.10.002
Supplementary material: http://cherry.chem.bg.ac.rs/handle/123456789/2975

DOI: 10.1016/j.jinorgbio.2018.10.002

ISSN: 0162-0134

WoS: 000452938900006

Scopus: 2-s2.0-85055090720

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URI

https://cherry.chem.bg.ac.rs/handle/123456789/2796

Collections

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Hemijski fakultet

TY - JOUR
AU - Bjelogrlić, Snežana K.
AU - Todorović, Tamara
AU - Cvijetić, Ilija
AU - Rodić, Marko
AU - Vujčić, Miroslava
AU - Marković, Sanja B.
AU - Araškov, Jovana
AU - Janović, Barbara
AU - Emhemmed, Fatihi
AU - Muller, Christian D.
AU - Filipović, Nenad R.
PY - 2019
UR - https://cherry.chem.bg.ac.rs/handle/123456789/2796
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. © 2018 Elsevier Inc.
T2 - Journal of Inorganic Biochemistry
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
VL - 190
SP - 45
EP - 66
DO - 10.1016/j.jinorgbio.2018.10.002
ER -

@article{
author = "Bjelogrlić, Snežana K. and Todorović, Tamara and Cvijetić, Ilija and Rodić, Marko and Vujčić, Miroslava and Marković, Sanja B. and Araškov, Jovana and Janović, Barbara and Emhemmed, Fatihi and Muller, Christian D. and Filipović, Nenad R.",
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. © 2018 Elsevier Inc.",
journal = "Journal of Inorganic Biochemistry",
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",
volume = "190",
pages = "45-66",
doi = "10.1016/j.jinorgbio.2018.10.002"
}

Bjelogrlić, S. K., Todorović, T., Cvijetić, I., Rodić, M., Vujčić, M., Marković, S. B., Araškov, J., Janović, B., Emhemmed, F., Muller, C. D.,& Filipović, N. R.. (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 Journal of Inorganic Biochemistry, 190, 45-66.
https://doi.org/10.1016/j.jinorgbio.2018.10.002

Bjelogrlić SK, Todorović T, Cvijetić I, Rodić M, Vujčić M, Marković SB, Araškov J, Janović B, Emhemmed F, Muller CD, Filipović NR. 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 Journal of Inorganic Biochemistry. 2019;190:45-66.
doi:10.1016/j.jinorgbio.2018.10.002 .

Bjelogrlić, Snežana K., Todorović, Tamara, Cvijetić, Ilija, Rodić, Marko, Vujčić, Miroslava, Marković, Sanja B., Araškov, Jovana, Janović, Barbara, Emhemmed, Fatihi, Muller, Christian D., Filipović, Nenad R., "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 Journal of Inorganic Biochemistry, 190 (2019):45-66,
https://doi.org/10.1016/j.jinorgbio.2018.10.002 . .