METAL-BASED COMPLEXES IN BIOLOGICAL SYSTEMS: IMPLICATIONS FOR THERAPEUTIC APPLICATIONS

Abstract

Metal-based complexes, and especially copper-containing systems, have been drawing growing attention due to their capacity to cause cellular homeostasis and regulated cell death; the transcriptomic consequences of copper-induced stress in cancer cells are largely uncharacterized, though. The present work investigated gene expression changes and pathway-level responses associated with copper exposure using high-throughput RNA sequencing data from CAL-27 cells treated with an elesclomol–copper complex and untreated controls. Following data normalization and quality assessment, differential expression analysis was performed with adjusted p < 0.05 and |log2FC| ≥ 1 as thresholds, and functional interpretation was conducted using Gene Ontology, pathway enrichment, and gene set enrichment analyses. Copper treatment produced a clear transcriptomic separation between conditions and resulted in 2,462 significantly differentially expressed genes, comprising 324 upregulated and 2,138 downregulated genes. Notably, stress- and metal-response genes such as HMOX1, MT1X, and HSPA1A were strongly induced, whereas proliferation-associated genes including PLK1, VIM, and FZD2 were suppressed. Enrichment analyses revealed significant involvement of p53 signaling, cell cycle regulation, apoptosis, mineral absorption, endoplasmic reticulum stress, and ferroptosis-related pathways, indicating coordinated disruption of cellular homeostasis. These findings demonstrate that copper-based treatment induces extensive transcriptomic reprogramming characterized by activation of stress-response mechanisms and inhibition of proliferative processes, supporting the therapeutic relevance of metal-based complexes in cancer biology.