This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
In Silico and In Vitro Evaluation of δ-cadinene from Decatropis bicolor as a Selective Inhibitor of Human Cell Adhesion and Invasion Proteins
by
, , , , , , , and
Iannel Reyes-Vidal
1
,
Ivan Tepale-Ledo
1,
Gildardo Rivera
2
,
Emma Ortiz-Islas
3,
Salvador Pérez-Mora
1,
David Guillermo Pérez-Ishiwara
1,
Yazmin Montserrat Flores-Martinez
1,
Maricarmen Lara-Rodríguez
1 and
María del Consuelo Gómez-García
1,* 1
Laboratorio de Biomedicina Molecular I, Programa de Doctorado en Ciencias en Biotecnología, Escuela Nacional de Medicina y Homeopatía (ENMyH), Instituto Politécnico Nacional, Mexico City 07320, Mexico
2
Laboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Reynosa 88710, Mexico
3
Laboratorio de Neurofarmacología Molecular y Nanotecnología, Instituto Nacional de Neurología y Neurocirugía “Manuel Velasco Suárez”, Mexico City 14269, Mexico
*
Author to whom correspondence should be addressed.
Cancers 2025, 17(17), 2839; https://doi.org/10.3390/cancers17172839
Submission received: 19 July 2025
/
Revised: 23 August 2025
/
Accepted: 26 August 2025
/
Published: 29 August 2025
(This article belongs to the Section Molecular Cancer Biology)
Simple Summary
Breast cancer remains an aggressive disease with limited therapeutic alternatives. In this study, we investigated the anticancer effects of δ-cadinene on the MDA-MB-231 breast cancer cell line. δ-cadinene significantly reduced cell viability, impaired invasive capacity, and altered cell morphology, while exerting minimal effects on normal MCF10-A cells. Computational approaches, including molecular docking and molecular dynamics simulations, revealed a strong and stable interaction between δ-cadinene and MMP-2, a key protein involved in cancer invasion. These findings suggest that δ-cadinene is a promising candidate for targeted breast cancer therapy modulating MMP-2.
Abstract
Background: 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 Decatropis bicolor 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. Objectives: To investigate the interaction of δ-cadinene with these proteins using in silico approaches and in vitro evaluations. Methods: 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. Results: 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. Conclusions: 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.
