Abstract

Abstract INTRODUCTION Glioblastoma is a brain tumor with a very poor prognosis that is highly resistant to treatment. Hiba (Thujopsis dolabrata) has been used as a building material because of its insect repellent effect and refreshing fragrance. In this study, we analyzed the antitumor effects of thujopsen, which is contained in the essential oil of hiba, and investigated its antitumor aroma therapy.Methods and RESULTS We investigated the anti-tumor aroma effect of hiba essential oil on glioblastoma cells (U251, T98G), gastric cancer cells (MKN45), and breast cancer cells (MCF7). The anti-tumor effect of hiba essential oil varied depending on the carcinoma, with strong inhibition of cell proliferation observed in MKN45, U251, and T98G cells. Hinokitiol in hiba essential oil has been reported to have antitumor effects, and we isolated and identified a new antitumor factor, thujopsene, by liquid chromatography analysis. In tumor cell proliferation assays, thujopsen inhibited tumor cell proliferation more rapidly and potently than hinokitiol. Comparing the reach of the two compounds, hinokitiol showed a broader anti-tumor effect than thujopsen. The expression of caspase-3 and caspase-9 was increased by thujopsen, and DARTS analysis identified PKM2 as an intracellular binding protein of thujopsen. DISCUSSION The present study revealed that thujopsen induces apoptosis via caspase-3 and caspase-9. Furthermore, unlike hinokitiol, thujopsen was suggested to exhibit antitumor effects mediated by PKM2. CONCLUSION Thujopsen is a low molecular weight compound and easily evaporates into the air, it is expected to be applied to a new glioblastoma therapy using "aroma".

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