DDDR-18. Antitumor Effects of Lemongrass Essential Oil and Citral in Glioblastoma: A Novel Inhalational Therapeutic Strategy

Abstract BACKGROUND Nearly two decades have passed since temozolomide was approved for the treatment of glioblastoma; however, patient prognosis remains extremely poor. Natural products have long served as a valuable source for drug discovery, and continued exploration of anticancer agents derived from natural compounds remains crucial. Plants produce both primary and secondary metabolites. While primary metabolites are essential for plant survival and are universally present, secondary metabolites vary across species and exhibit a wide range of chemical structures and biological activities, including anticancer effects. Essential oils, which are complex mixtures of plant-derived secondary metabolites, have been reported to induce apoptosis and cell cycle arrest in cancer cells. In this study, we investigated the antitumor potential of lemongrass essential oil and its major component, citral, as a novel therapeutic approach for glioblastoma. METHODS Human glioma cell lines (U251, T98G) and a murine glioma cell line (RSV-M) were used. Antiproliferative effects of lemongrass essential oil vapor and direct citral application were evaluated in vitro. For in vivo analysis, a syngeneic orthotopic murine glioma model (RSV-M) was employed. The antitumor effect of lemongrass essential oil inhalation was assessed using Kaplan–Meier survival analysis and tumor volume measurements. RESULTS Exposure to lemongrass essential oil vapor suppressed cell proliferation in all glioma cell lines tested, with greater inhibition observed at shorter distances from the vapor source. Direct application of citral to culture wells led to dose- and time-dependent growth inhibition in all cell lines. In vivo, mice that inhaled lemongrass essential oil (n=6) demonstrated significantly prolonged survival compared to control mice (n=6; p=0.0102) and significantly reduced tumor volumes (p=0.0022). CONCLUSION Lemongrass essential oil and its main constituent, citral, exhibit potential antitumor activity against glioblastoma. These findings suggest that inhalation of volatile natural compounds may serve as a novel, noninvasive therapeutic strategy for the treatment of glioblastoma.