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Başlık: Synthesis, biological characterization and evaluation of molecular mechanisms of novel copper complexes as anticancer agents
Yazarlar: Açılan, Ceyda
Adıguzel, Zelal
Ribeiro, Nádia
Correia, Isabel
Pessoa, João Costa
Uludağ Üniversitesi/Fen-Edebiyet Fakültesi/Biyoloji Bölümü.
Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyokimya Anabilim Dalı.
0000-0002-3781-6834
Cevatemre, Buse
Karakaş, Didem
Ulukaya, Engin
AHD-2050-2022
L-6682-2018
K-5792-2018
55693788600
56422040600
6602927353
Anahtar kelimeler: Biochemistry & molecular biology
Biophysics
Copper complexes
Schiff base compounds
Phenanthroline
Interactions with DNA
Anti-cancer drugs
Mechanism of cytotoxicity of Cu-compounds
Cells in-vitro
Salicylideneamino acidato complexes
Human cancer-cells
Dna-binding
Heterocyclic bases
Crystal-structures
Cleavage activity
Topoisomerase inhibition
Chemical nucleases
Oxidative stress
Yayın Tarihi: Şub-2017
Yayıncı: Elsevier
Atıf: Açılan, C. vd. (2017). ''Synthesis, biological characterization and evaluation of molecular mechanisms of novel copper complexes as anticancer agents''. Biochimica et Biophysica Acta General Subjects, 1861(2), 218-134.
Özet: Background: To overcome the hurdles of cisplatin, majorly its toxicity and resistance, there has been extensive search for alternative anti-cancer metal-based compounds. Here, three Cu(II)-complexes, Cu(Sal-Gly)(phen), Cu(Sal-Gly)(pheamine), Cu(Sal-Gly)(phepoxy) are characterized for their interaction with DNA, cytotoxicity and mechanism of action. Methods: The binding ability of the complexes to Calf-Thymus DNA was evaluated by competition fluorescence studies with thiazole-orange, UV-Vis and circular dichroism spectroscopic titrations. Cytotoxicity was evaluated by MTT analysis. The DNA damage was analyzed through cleavage of supercoiled DNA via agarose gel-electrophoresis, and 8-oxo-guanidine and gamma H2AX staining in cells. Apoptosis was detected via DNA condensation/fragmentation, mitochondrial membrane potential, Annexin V staining and caspase 3/7 activity. Formation of reactive oxygen species was determined by DCFDA- and GSSG/GSH-analysis. Results: Binding constants to DNA were evaluated as 1.7 x 10(6) (Cu(Sal-Gly)(phen)), 2.5 x 10(6) (Cu(Sal-Gly)(pheamine)) and 3.2 x 10(5) (Cu(Sal-Gly)(phepoxy)). All compounds induced DNA damage. Apoptosis was the main form of cell death. There was an increase in ROS, which is most likely responsible for the observed DNA-damage. Although the compounds were cytotoxic to all tested cancer cell lines, only Cu(Sal-Gly)(pheamine) displayed significantly lower toxicity towards non-cancer cells, its associated phenotypes differing from the other two Cu-complexes. Thus, Cu(Sal-Gly)(pheamine) was further assayed for molecular changes in response to drug treatment using a custom designed RT-qPCR array. Results showed that Harakiri was significantly upregulated. Presence of p53 was not required for apoptosis in response to Cu-complexes. Conclusions and general significance: These Cu-complexes, namely Cu(Sal-Gly)(pheamine), may be considered promising anticancer agents with activity in cancer cells even with deficient p53 status.
URI: https://doi.org/10.1016/j.bbagen.2016.10.014
https://www.sciencedirect.com/science/article/pii/S0304416516303890
http://hdl.handle.net/11452/29316
ISSN: 0304-4165
1872-8006
Koleksiyonlarda Görünür:Scopus
Web of Science

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