Anti-Tumor Potential of Frankincense Essential Oil and Its Nano-Formulation in Breast Cancer: An In Vivo and In Vitro Study

<b>Background/Objective:</b> Breast cancer remains the most common malignancy among women worldwide, contributing to high morbidity and mortality rates. Many anti-cancer drugs have been derived from medicinal plants, and frankincense from <i>Boswellia carterii</i> is notable for its anti-inflammatory, anti-neoplastic, and anti-carcinogenic properties. Using gas chromatography/mass spectrometry (GC/MS), 48 components were identified in <i>B. carterii</i> essential oil, and the major constituent was α-pinene (35.81%). <b>Method:</b> In this study, we investigated the anti-tumor effects of frankincense essential oil (FEO) and its nano-formulation with chitosan (FEO-CSNPs) using in vitro breast cancer models (MCF-7, MDA-MB-231, and 4T1 cells) and in vivo mouse mammary carcinoma (4T1) models (Balb/c). <b>Results:</b> The results showed significant reductions in cell viability. At 10 μg/mL, the FEO showed the highest reduction in the C-166 cells, while at 100 μg/mL, the FEO exhibited a stronger cytotoxicity in the MDA-MB-231 and 4T1 cells compared to the FEO-CSNPs and CSNPs. The FEO-CSNPs exhibited cell growth arrest in the S, G2/M, and G1/S phases in the MCF-7, MDA-MB-231, and 4T1 cell lines (36.91%, 23.12%, and 33.58%), in addition to increased apoptosis rates in the MCF-7, MDA-MB-231, and 4T1 cell lines (33.04%, 36.39%, and 42.19%). The wound healing assays revealed a decreased migratory ability in the treated cells. The in vivo experiments in the balb/c mice demonstrated a reduction in the tumor volume, with a histopathological analysis confirming extensive tumor necrosis. Moreover, the FEO and FEO-CSNPs showed notable antioxidant and arginase activity. The gene expression analysis via qPCR indicated the upregulation of tumor suppressor genes and the downregulation of oncogenes. <b>Conclusions:</b> These findings suggest that FEO and its nano-formulation, particularly in the form of FEO-CSNPs as an oral formulation, display enhanced efficacy, warranting further preclinical and clinical research to develop innovative treatment strategies.