Elucidating Anti‐Breast Cancer Potential of Citrus medica Essential Oil: Targeting VEGFR2 and HER2 Receptors by In Silico Molecular Docking Analysis

Vollständiger Abstract

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ABSTRACT Breast cancer is one of the most common cancers that affects women globally. The anti‐breast cancer potential of Citrus medica leaf essential oil (CMeLO) remains largely unknown, despite Citrus medica being a medicinally significant aromatic plant long used to treat a variety of illnesses. Consequently, this investigation assessed the antiproliferative activity of CMeLO against the human breast cancer cell line (MCF‐7). Gas chromatography–mass spectrometry (GC–MS) chemical profiling of CMeLO showed that oxygenated monoterpenes (64.7%) and monoterpene hydrocarbons (28.4%) constituted majority of the essential oil composition. Limonene (26.36%), geranial (16.73%), neral (14.97%), geraniol (6.79%) and nerol (7.06%) were the main constituents found. With an IC 50 value of 92.91 μg/mL, the MTT assay in vitro cytotoxicity assessment revealed strong antiproliferative activity. Additionally, DNA fragmentation analysis revealed that CMeLO induces irreversible DNA damage, resulting in cell death via apoptosis. In silico molecular docking studies were conducted against Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) and Human Epidermal Growth Factor Receptor 2 (HER2), two important therapeutic targets in breast cancer, to investigate potential molecular mechanisms underlying its anticancer activity. Citronellal, neral, nerol and neryl acetate interacted favourably with HER2, while β ‐bisabolol, ( E )‐phytol, geranyl acetate and neryl acetate demonstrated strong binding affinities towards VEGFR2. These results imply that CMeLO may inhibit angiogenesis and induce apoptosis to produce anticancer effects. Additionally, favourable pharmacokinetic characteristics for the main volatile constituents were predicted by Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET). These findings underscore CMeLO as a promising natural source of bioactive compounds for breast cancer treatment. Nonetheless, more in vivo and mechanistic studies are needed to confirm its efficacy, safety, and molecular targets prior to clinical application.