In Vitro Anticancer Activity and Integrated Multi-Target Computational Analysis of Ylang-Ylang Essential Oil Against Breast Cancer

Ylang-ylang essential oil (YEO), obtained from Cananga odorata, contains chemically diverse constituents with potential anticancer activity that warrants further investigation. This study investigated the anti-breast-cancer potential of YEO through an integrated experimental and computational approach. The essential oil was chemically characterized by gas chromatography–mass spectrometry, and its in vitro cytotoxic activity was evaluated against ER-positive MCF-7 and triple-negative MDA-MB-231 and MDA-MB-436 breast-cancer cell lines using the MTT assay. Peripheral blood mononuclear cells were included as a preliminary model for assessing cytotoxic selectivity toward non-tumoral cells. To generate hypotheses concerning possible molecular interactions, identified constituents were evaluated against three breast-cancer-relevant targets: estrogen receptor alpha (ER-α), epidermal growth factor receptor (EGFR), and poly(ADP-ribose) polymerase 1 (PARP1). The computational workflow included a structural confidence assessment based on AlphaFold 2, together with CNN-assisted Gnina docking, Glide docking, and in silico ADMET profiling. The in vitro experiments showed that YEO had biological activity against breast-cancer cells, and the computational analyses showed that the ligand profiles were dependent on the target. Gnina identified trans-geranylgeraniol, farnesyl-decanoate and linalool as the top candidates for ER-α, EGFR and PARP1, respectively, while Glide pointed out δ-cadinene for ER-α, benzyl salicylate for EGFR and benzyl benzoate for PARP1. Both benzyl benzoate and α-cadinol also had potentially favorable multi-target binding profiles. The ADMET analysis found that several components had acceptable drug-likeness, but the high lipophilicity of some sesquiterpenes might limit their pharmacokinetic behavior. Overall, the results support the prioritization of selected YEO constituents as candidates for further investigation of potential multi-target anticancer activity. Nevertheless, the docking results remain predictive and do not demonstrate direct target inhibition or molecular synergy. Further biochemical, mechanistic, pharmacokinetic, and in vivo studies are needed to evaluate the biological relevance and translational potential of the prioritized constituents.