Bioactivities of Bulgarian Rose Essential Oil in In Vitro and In Vivo Cancer Models and In Silico Target Prediction

Background/Objectives: Bulgarian Rose Essential Oil (BREO), obtained from Rosa damascena Mill., is a complex mixture of bioactive compounds with diverse pharmacological properties. This study investigated the bioactivities of BREO in cancer models using experimental and in silico approaches. Methods: Phytochemical composition of BREO was characterized by GC-FID. Antiproliferative activity was evaluated against HeLa, PC-3, and Ehrlich Ascites Carcinoma (EAC) cells, with HaCaT keratinocytes as non-tumorigenic reference. Apoptosis and cellular responses were assessed in EAC cells by fluorescence microscopy. Toxicity and anticancer effects of BREO were investigated in murine model of Ehrlich carcinoma using histopathological, hematological, and immunohistochemical analyses. Serum Interleukin-1β and Interleukin-17α levels were determined. Molecular docking of three major BREO constituents, geraniol, citronellol, and nerol, against IKKβ, HER2, and ERα was performed. Results: BREO exhibited concentration-dependent antiproliferative activity, with EAC cells showing the greatest sensitivity with IC50 value of 195 µg/mL. Fluorescence microscopy revealed morphological changes consistent with cell death and alterations in mitochondrial membrane potential. In vivo, BREO treatment was associated with extensive necrotic and apoptotic areas within tumors and changes in Ki-67 and hormone receptor expression. Serum IL-1β levels were comparable between BREO- and 5-fluorouracil-treated groups, whereas no significant differences in IL-17α levels were observed. Molecular docking revealed favorable binding of all three constituents within active sites of the respective targets with binding energies of −5.3 kcal/mol, −6.3 kcal/mol, and −6.0 kcal/mol, respectively. Conclusions: BREO exhibited anticancer potential, accompanied by cellular, morphological, and molecular changes associated with cancer cell death, warranting further mechanistic studies.