Apoptosis-inducing effects of sterols from the dried powder of cultured mycelium of Cordyceps sinensis.

The methanolic extract and its ethyl acetate-soluble fraction from the dried powder of cultured Cordyceps sinensis mycelium showed cytotoxic effects on promyelocytic leukemia HL-60 cells. Sitosterol (1), 5 alpha,8 alpha-epidioxy-22E-ergosta-6,22-dien-3beta-ol (2), 5 alpha,8 alpha-epidioxy-22E-ergosta-6,9(11),22-trien-3beta-ol (3), 5 alpha,6 alpha-epoxy-5 alpha-ergosta-7,22-dien-3beta-ol (4), and ergosterol (5) were isolated from the ethyl acetate fraction. Among the isolated compounds, 2-4 with a peroxide ring or an epoxide ring showed substantial cytotoxic activity with IC(50) values of 7.3-7.8 microg/ml, but 1 and 5 showed only moderate activity. Furthermore, apoptosis of HL-60 cells was observed 24 h after treatment with 2-4 (10, 20 microg/ml) using the TdT-mediated dUTP nick-end labeling method, and their apoptosis-inducing activities are suggested to be dependent on the activation of caspases-3/7. To the best of our knowledge, this is the first report of the isolation of sterol constituents (1-5) from cultured C. sinensis mycelium.