Anti-tumor effects of Cinnamomum camphora essential oil in breast cancer via NOX4 modulation by (+)-2-bornanone

BACKGROUND: Breast cancer (BC) is the most prevalent malignancy among women. Cinnamomum camphora essential oil (CCEO) has shown potential in cancer therapy, but its anti-tumor components and mechanisms in BC remain unclear. NADPH oxidase 4 (NOX4) is an important producer of reactive oxygen species (ROS), driving cancer progression and serving as a potential therapeutic target. PURPOSE: To investigate the anti-tumor activity of CCEO, characterize its active compounds, and clarify its molecular mechanisms. METHODS: The anti-tumor effects of CCEO were assessed in BC cell lines via MTT assays, western blot, and flow cytometry. The modulation of signaling pathways was analyzed via western blot and RT-qPCR. Xenograft tumor models were employed to evaluate efficacy and safety in vivo. Gas chromatography-mass spectrometry (GC-MS) was used to identify major constituents of CCEO, and NOX4 overexpression assays were conducted to explore molecular mechanisms. RESULTS: CCEO exhibited significant anti-tumor activity both in vitro and in vivo by inducing apoptosis and senescence, decreasing intracellular ROS levels, inhibiting migration and invasion, and causing cell cycle arrest. GC-MS analysis identified (+)-2-Bornanone as the predominant active component responsible for anti-tumor effects. Mechanistically, (+)-2-Bornanone suppressed NOX4 expression, which inhibited the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway, ultimately suppressing tumor progression. CONCLUSION: The anti-tumor effects of CCEO in triple-negative breast cancer (TNBC) are principally mediated by (+)-2-Bornanone, which inhibits the MAPK/ERK pathway via NOX4 downregulation. These findings reveal a novel anti-tumor mechanism and provide a strong rationale for further developing (+)-2-Bornanone as a promising natural therapeutic agent for BC treatment.