Anti-Tumor-Promoting Activities of Euglobals from Eucalyptus Plants

To search for possible anti-tumor-promoters (chemopreventive agents), we carried out a primary screening of 21 euglobals (acylphloroglucinol-monoterpene or -sesquiterpene structures) isolated from the juvenile leaves of five species of Eucalyptus plants using an in vitro synergistic assay system. Of these compounds, euglobal-G1-G5 (1-5), -Am-2 (15) and -III (16) exhibited significant inhibitory effects on Epstein-Barr virus (EBV) activation induced by the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). Furthermore, the effects of compounds 1 and 16 on the cell cycle of Raji cells were also examined by a flow cytometer, and both compounds 1 and 16 exhibited strong inhibition on the effect of the cell cycle induced by TPA. These two euglobals (1 and 16) exhibited remarkable anti-tumor-promoting effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test.