Document Type

Article

Disciplines

3. MEDICAL AND HEALTH SCIENCES, Oncology

Publication Details

https://www.sciencedirect.com/science/article/pii/S0162013423002659

Hollie Jenkins, Louise MacLean, Siobhán McClean, Gordon Cooke, Michael Devereux, Orla Howe, Marcos D. Pereira, Nóra V. May, Éva A. Enyedy, Bernadette S. Creaven, Structural and solution speciation studies on selected [Cu(NN)(OO)] complexes and an investigation of their biomimetic activity, ROS generation and their cytotoxicity in normoxic, hypoxic and anoxic environments in MCF-7 breast cancer-derived cells, Journal of Inorganic Biochemistry, Volume 249, 2023, 112383, ISSN 0162-0134,

https://doi.org/10.1016/j.jinorgbio.2023.112383.

Abstract

Reactive oxygen species(ROS) generation with subsequent DNA damage is one of the principle mechanisms of action assigned to copper-based anticancer complexes. The efficacy of this type of chemotherapeutic may be reduced in the low oxygen environment of tumours. In this study the cytotoxicity of three complexes, [Cu(dips)(phen)] (1), [Cu(ph)(phen)]·2H2O (2) and [Cu(ph)(bpy)]·H2O (3) (disp: 3,5-diisopropylsalicylate, phen: 1,10- phenanthroline, ph: phthalate, bpy: 2,2′-bipyridyl) were assessed for anticancer activity in the breast-cancer derived MCF-7 line under normoxic, hypoxic and anoxic conditions. In an immortalised keratinocyte HaCaT cell line, the cytotoxicity of complexes 2 and 3 was significantly reduced under both normoxic and hypoxic conditions, whilst the cytotoxicity of complex 1 was increased under hypoxic conditions. The ability of the complexes to generate ROS in the MCF-7 cell line was evaluated as was their ability to act as superoxide dismutase(SOD) and catalase mimics using a yeast cell assay. ROS generation was significant for complexes 2 and 3, less so for complex 1 though all three complexes had SOD mimetic ability. Given the ternary nature of the complexes, solution speciation studies were undertaken but were only successful for complex 3, due to solubility issues with the other two complexes. The concentration distribution of various species, formed in aqueous solution, was evaluated as a function of pH and confirmed that complex 3 is the dominant species at physiological pH in the mM concentration range. However, as its concentration diminishes, it experiences a progressive dissociation, leading to the formation of binary complexes of bpy alongside unbound phthalate.

DOI

https://doi.org/10.1016/j.jinorgbio.2023.112383

Funder

Science Foundation Ireland –Investigator Programme SFI/12/IP/1390; Irish Reseach Council Postgraduate Awards (EM 200701); Centre of Applied Science for Health, TU Dublin; D24 FKT9; National Research, Development and Innovation Office (Hungary) TKP-2021-EGA-32 and by the “Lendület” Programme (ELKH, LP2019-6/2019) (EAE); K124544; FAPERJ (Edital N.° 43/2013, Programa de Apoio ao Doutorado-Sanduíche Reverso), CNPq and CAPES fundings; Programme for Research in Third Level Institutions (PRTLI) Cycle 5 under the supervision of Dr. Úna Prendergast; European Regional Development Fund (ERDF)

Creative Commons License

Creative Commons Attribution-Share Alike 4.0 International License
This work is licensed under a Creative Commons Attribution-Share Alike 4.0 International License.

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