Integrative In Vitro and Computational Analysis of Lavandula angustifolia Essential Oil Reveals Leo‐3 as a Promising Therapeutic Agent against Lung Cancer

ABSTRACT Despite advances in targeted therapies, non‐small cell lung cancer (NSCLC) continues to suffer from treatment resistance and limited therapeutic durability. This highlights the need for novel, multi‐target agents with improved safety profiles. Natural products, particularly essential oils, remain underexplored in NSCLC with respect to integrated mechanistic validation. Lavandula angustifolia , a widely used medicinal plant, demonstrates potent cytotoxic effects against A549 lung cancer cells, primarily due to its major bioactive compound, LeO‐3 (linalool). In this study, lavender oil was extracted via hydro‐distillation and subjected to a comprehensive set of analyses including, MTT assay, colony formation assay, wound healing assay (WHA), quantitative real‐time PCR (qRT‐PCR), in silico molecular docking, and protein‐protein interaction network analysis. The oil significantly reduced cell viability in a dose‐dependent manner and inhibited clonogenic potential and cell migration, suggesting strong anti‐proliferative and anti‐metastatic activities. Molecular assays revealed downregulation of key pro‐inflammatory and metastatic genes such as IL‐1α, TNF‐α, IL‐6, COX‐2, and VIM. In silico studies confirmed stable binding of LeO‐3 to TNF‐α, while STRING network analysis identified it as part of a central inflammatory signaling hub. Additionally, ADMET profiling supported LeO‐3's drug‐likeness and oral bioavailability. Collectively, these findings provide mechanistic evidence supporting Leo‐3 as a promising natural lead compound for NSCLC and establish a foundation for further preclinical evaluation and combination‐based therapeutic strategies.