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

Autor: Muller, Christian D., Bjelogrlić, Snežana, Todorović, Tamara, Cvijetić, Ilija, Rodić, Marko, Vujčić, Miroslava, Marković, Marko, Araškov, Jovana, Janović, Barbara, Emhemmed, Fathi, Muller, Christian, Filipović, Nenad
Přispěvatelé: Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), National Cancer Research Center of Serbia, Laboratoire d'Innovation Thérapeutique (LIT), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Cooltech Applications, Cooltech
Rok vydání: 2019
Předmět:
Zdroj: Journal of Inorganic Biochemistry
Journal of Inorganic Biochemistry, Elsevier, 2019, 190, pp.45-66. ⟨10.1016/j.jinorgbio.2018.10.002⟩
ISSN: 0162-0134
DOI: 10.1016/j.jinorgbio.2018.10.002⟩
Popis: 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. 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]
Databáze: OpenAIRE
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