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

Abstract

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.