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Anticancer and antimetastatic activity of copper(II)-tropolone complex against human breast cancer cells, breast multicellular spheroids and mammospheres

2019; Elsevier BV; Volume: 204; Linguagem: Inglês

10.1016/j.jinorgbio.2019.110975

1873-3344

Lucía M. Balsa, María C. Ruiz, Lucía Santa Maria de la Parra, Enrique J. Baran, Ignácio E. León,

Synthesis and Characterization of Heterocyclic Compounds

The goal of this work was to display the anticancer and antimetastatic activity of a copper(II) with tropolone (trp), complex [Cu(trp)2] toward human breast cancer cells in monolayer (2D) and spheroids (3D). Cytotoxicity assays against MCF7 (IC50(complex) = 5.2 ± 1.8 μM, IC50(CDDP) = 19.3 ± 2.1 μM) and MDA-MB-231 (IC50(complex) = 4.0 ± 0.2 μM, IC50(CDDP) = 27.0 ± 1.9 μM) demonstrate that [Cu(trp)2] exert greater antitumor potency than cisplatin (CDDP) on 2D and 3D human breast cancer cell models. Besides, [Cu(trp)2] inhibits cell migration by reducing the metalloproteinases activities and the compound undergoes the breast cancer cells to apoptosis at lower concentrations (2.5–10 μM). Moreover, [Cu(trp)2] overcame CDDP presenting an IC50 value 26-fold more lower against breast multicellular spheroids ((IC50(complex) = 4.9 μM, IC50(CDDP) = 130 μM)). Also, our results showed that [Cu(trp)2] inhibited the cell migration and cell invasion of breast multicellular spheroids, showing that [Cu(trp)2] exhibited antimetastatic properties. On the other hand, [Cu(trp)2] reduced mammosphere forming capacity affecting the size and number of mammospheres. Taken together, [Cu(trp)2] exhibited anticancer and antimetastatic properties on monolayer (2D) and spheroids (3D) derived from human breast cancer cells.