ArticleJournal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry2026
Role of the NHE1 exchanger in the antitumor effects of copper(II) complexes and phenanthroline derivatives.
Article in Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Three copper(II) complexes containing 1,10-phenanthroline: [CuCl2(phen)]·0.5H2O (1), neocuproine [CuCl2(neo)]·0.75 H2O (2) and tetramethyl-phenanthroline [CuCl2(tmp)]·H2O (3) as the primary ligand and another three copper(II) complexes with L-Ala-Phe dipeptide as auxiliary ligand: [Cu(L-Ala-Phe)(phen)]·4H2O (4), [Cu(L-Ala-Phe)(neo)]·3H2O (5) and [Cu(L-Ala-Phe)(tmp)]·3H2O (6), inhibited cell viability in the MCF-7 cell line, both in the monolayer and spheroid models. The pair with tmp displayed a better selectivity index than cisPt and non-cytotoxicity-related ROS induction and apoptosis in the monolayer model. Cell proliferation was affected by all compounds in a concentration-dependent manner. Cell viability on spheroids showed a reduction from 1 µM, with IC50 values that were half those of cisplatin. All copper complexes, except for 1, showed DNA damage at a concentration below IC50. Our study revealed that all compounds inhibited sodium-hydrogen exchanger (NHE1) activity in MCF-7 cells. However, only complexes containing the dipeptide could extend their effect on cell migration and metalloprotease MMP-9 activity. Western Blot analysis showed that metalloproteases MMP-2, MMP-9, and NHE1 expression was also affected when MCF-7 cells were treated with the six compounds. Overall, our results reveal an antitumor effect of all copper(II) complexes studied in breast cancer cells and a fundamental role of NHE1 in cell migration.
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