Comparative Biological Evaluation of Catechin and Its Previously Characterized Zn(II) and Cu(II) Coordination Preparations in U2-OS Cells

Background/Objectives: Osteosarcoma (OS) is an aggressive cancer with high prevalence in children, adolescents and young adults. Catechin (CAT) presents broad-spectrum therapeutic potential, with previously studied anticancer properties. Metal complexation with zinc(II), Zn(II), and copper(II), Cu(II), emerged as a promising strategy for the development of improved metallodrugs against OS. The objective of this study was to comparatively evaluate the in vitro anticancer effect of CAT, catechin-zinc(II), CAT-Zn(II), and catechin-copper(II), CAT-Cu(II), in U2-OS cells used as 2D OS models. Methods: To achieve this, the impact of CAT and its metal complexes on the viability, morphology, proliferation, clonogenic capacity, migratory ability and apoptotic cell death in U2-OS cells was evaluated. Results: Our findings revealed that CAT-Cu(II) displays a comparable behavior to CAT, with low cytotoxicity, but strong anti-clonogenic and anti-migratory activities. In contrast, CAT-Zn(II) exerted prominent anti-tumor activity in vitro, with concentration-dependent reduction in cell viability (from 88.34% at 0.1 mM, to 5.50% at 0.5 mM) and proliferation inhibition, strong suppression of colony formation and migration rates (below 10% and 50%, respectively), marked alterations in mitochondrial membrane potential and apoptosis-associated changes. These biological effects were correlated with KI67, metalloproteinase-2 (MMP-2) and vimentin downregulation, and BAX upregulation. Conclusions: The investigated catechin–metal preparations showed distinct biological effects in U2-OS cells. CAT-Zn(II) caused the greatest reductions in cell viability and proliferation, along with mitochondrial alterations and apoptosis-associated changes. CAT-Cu(II), by contrast, had limited cytotoxicity but reduced colony formation and wound closure. These findings support further study of CAT-Zn(II) in additional experimental models.