Inhibitory Effect of Euphol, a Triterpene Alcohol from the Roots of Euphorbia kansui , on Tumour Promotion by 12- O -Tetradecanoylphorbol-13-acetate in Two-stage Carcinogenesis in Mouse Skin

Abstract

The anti-inflammatory activity of euphol, twelve other triterpene alcohols and sitosterol-β-D-glucopyranoside, isolated from the dichloromethane extract of the roots of Euphorbia kansui, has been evaluated in mice with inflammation induced by 12-O-tetradecanoyl-phorbol-13-acetate (TPA).TPA (1.7 nmol; 1.0 μg/ear) was dissolved in acetone and 10 μL delivered to the inner and outer surfaces of the right ear of ICR mice. A triterpene alcohol, sterol glucoside or vehicle (20 μL; chloroform—methanol 1: 1), was applied topically approximately 30 min before each TPA treatment. The ear thickness was measured before treatment and then oedema was measured 6 h after TPA treatment.For the two-stage carcinogenesis experiment, initiation was accomplished by administration of a single topical application of 7,12-dimethylbenz[a]anthracene (DMBA; 195 nmol; 50 μg/mouse) to the shaved backs of mice. Promotion was with 1.7 nmol (1.0 μg) TPA, applied twice weekly to the same shaved area, begun one week after the initiation. Euphol (2.0 μmol; 853 μg), or its vehicle (acetone-dimethylsulphoxide, 9:1; 100 μL), was applied topically 30 min before each TPA treatment. The number and diameter of skin tumours were measured every other week for 20 weeks.All the compounds were found to possess marked inhibitory activity and their 50% inhibitory dose for TPA-induced inflammation was 0.2–1.0 mg/ear. Topical application of euphol (2.0 μmol; 853 μg/mouse) markedly suppressed the tumour-promoting effect of TPA (1.7 nmol; 1.0 μg/mouse) in mouse skin initiated with DMBA.