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
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Rodić, M. V.
Marković, Sanja B.
Muller, C. D.
Filipović, N. R.
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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...th 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.
Кључне речи:Apoptosis / Cancer stem cells / Cd(II) complex / DNA interactions / HSA interactions / Hydrazones
Извор:Journal of Inorganic Biochemistry, 2019, 190, 45-66
- Интеракције природних производа, њихових деривата и комплексних једињења са протеинима и нуклеинским киселинама (RS-172055)
- 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