Evaporated fraction of thujopsene from Thujopsis dolabrata starves cancer cells via PKM2 Anti-tumor effect of the volatile components of Thujopsis dolabrata

Abstract Objective Many cancer patients need for new treatment options with lower side effects. Herein, we report on the antitumor effect of thujopsene derived from the volatile components of Thujopsis dolabrata(asunaro). Methods The antitumor effect of the asunaro essential oil was analyzed using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay and in vivo cancer metastasis model. Thujopsene was isolated from asunaro essential oil by liquid chromatography, and the tumor growth inhibitory mechanism of thujopsene was assessed using Western blotting and DARTS (Drug affinity responsive target stability) analysis. Results The volatile components of asunaro essential oil exhibited an antitumor effect on MCF7 and SKBR3 breast cancer cells as well as on MKN45 gastric and DLD1 colon cancer cells. Thujopsene was identified as an antitumor factor that tended to have a stronger tumor growth inhibitory effect. Pyruvate kinase M2 (PKM2) was found to be associated with thujopsene in cancer cells. The reaction of thujopsene with MKN45 cells reduced intracellular lactate production. These results indicate that thujopsene binds to PKM2 in cancer cells and inhibits the nutritional metabolic pathway, and causing apoptosis. In conclusion, thujopsene may suppress tumor growth and metastasis by inhibiting the trophic metabolism pathway of cancer cells.