Quercetin and Citreorosein from Halodule uninervis Leaf Show the Best Binding Against Breast Cancer Targets AKT1, EGFR, and ESR1.

Introduction: The marine ecosystem, known for its diverse biochemistry and organisms adapted to harsh environments, contains numerous plants with promising anticancer potential. Halodule uninervis, a seagrass, contains a variety of bioactive compounds that provide various pharmacological properties. However, its potential anticancer effects against breast cancer remain largely unexplored.

Methods: HRLC-MS analysis was conducted to identify the phytochemicals in the ethanolic extract of H. uninervis leaves. Several publicly available databases, including SEA, STP, MALACARDS, DISGENET, and OMIM, were used to identify target genes. Protein-protein interaction (PPI) networks, gene ontology, and pathway analysis were carried out through the STRING and DAVID databases. Molecular docking was performed by Autodock Vina, while molecular dynamics (MD) simulations and MMPBSA analyses were conducted using GROMACS, demonstrating the stability of the complexes up to 200 ns.

Results: The top five therapeutically active phytochemicals were Quercetin, Arborinine, Methyl 3,4,5- trimethoxycinnamate, Citreorosein, and Scopolin. The five hub genes, AKT1, EGFR, TNF, ESR1, and GAPDH, were found by network analyses. Molecular docking and MD simulation demonstrate that Quercetin and Citreorosein are the best phytochemicals exhibiting the highest affinities to breast cancer targets AKT1, EGFR, and ESR1.

Discussion: For the first time, this in-silico study investigates the potential of citreorosein and quercetin, two phytochemicals predominantly found in H. uninervis leaves, to inhibit the activity of AKT1, EGFR, and ESR1. However, as these results are based on predictive computational analyses, further experimental validation is necessary to confirm their precise mechanisms of action.

Conclusion: Phytochemicals, namely Quercetin and Citreorosein, may have an impact on the progression of breast cancer by binding to the key targets AKT1, ESR1, and EGFR.