Therapeutic potential of monoterpene α-thujone, the main compound of Thuja occidentalis L. essential oil, against malignant glioblastoma multiforme cells in vitro.
Thuja occidentalis L. is indigenous for Northern America and commonly cultivated in Europe. Raw materials obtained from this tree are widely applied in the ethnomedicine and phytotherapy of numerous ailments, incl. scurvy, cystitis, rheumatism and cancer. Despite wide medicinal applications of Thuja occidentalis, still little is known on its therapeutic potential in tumor treatment. α-thujone is the main component of Thuja occidentalis essential oil, which has been suggested to possess anti-tumor activities. This monoterpene easily penetrates the blood-brain barrier. Therefore, we examined its effects on the malignancy of glioblastoma multiforme (GBM) cells, with the special emphasis on the mechanisms of its effect on cell viability and invasiveness. α-thujone exerted the attenuating effect on the viability and proliferation of GBM cells when administered at the concentrations between 100 and 500 µg/ml (660 µM - 3.2 mM). This effect was correlated with the induction of apoptosis in GBM cell populations and with considerable inhibition of GBM cells motility. Mechanistic analyses demonstrated the induction of oxidative stress and autophagy in α-thujone-treated tumor cells, whereas normal astrocytes displayed considerably lower sensitivity to α-thujone. Our observations demonstrate that α-thujone exerts pro-apoptotic and anti-invasive effects on GBM cells. They confirm the potential of α-thujone for the treatment of glioblastoma multiforme.