In Silico and In Vitro Evaluation of δ-cadinene from Decatropis bicolor as a Selective Inhibitor of Human Cell Adhesion and Invasion Proteins

<b>Background</b>: Breast cancer is a complex, multifactorial malignancy characterized by the uncontrolled proliferation of epithelial cells, with certain subtypes exhibiting resistance to conventional therapies. Plant-derived essential oils have been proposed as potential anticancer agents due to their bioactive compounds. Recent studies have demonstrated that <i>Decatropis bicolor</i> essential oil exhibits activity against breast cancer, attributed to diverse secondary metabolites such as δ-cadinene. Aberrant expression of adhesion and invasion proteins, including MMPs, CD44, N-cadherin, and ZEB-2, are key signs of breast cancer progression and metastasis; they represent relevant molecular targets. <b>Objectives</b>: To investigate the interaction of δ-cadinene with these proteins using in silico approaches and in vitro evaluations. <b>Methods</b>: In silico analyses were conducted to assess the interaction and stability of δ-cadinene with target proteins. In vitro assays, including cytotoxicity, morphological analysis, and cell invasion assays, were performed using MDA-MB-231 and MCF10-A cell lines. <b>Results</b>: Interaction analysis suggest that δ-cadinene interacts with key catalytic residues in MMP-2, sharing features with Quercetin. Blind docking revealed a second high-affinity site in the Fibronectin type II domain. Molecular dynamics simulations confirmed the stability of these complexes. In vitro studies showed that δ-cadinene significantly reduced MDA-MB-231 cell viability in a concentration-dependent manner, without affecting MCF10-A cells, and significantly inhibited invasion and MMP-2 activity after 24 h. <b>Conclusions</b>: δ-cadinene exhibits selective cytotoxic and anti-invasive activity in MDA-MB-231 cells, likely through dual inhibition of the catalytic and adhesion domains of MMP-2. These findings support δ-cadinene as a potential candidate for future therapeutic development in metastatic breast cancer.