2008 Volume 16 Issue 4 Pages 143-148
We have reported previously that ethyl acetate-extracts from the fruiting body of a Japanese edible mushroom, Buna-shimeji (Hypsizigus marmoreus), exhibited strong anti-tumor activities against tumorbearing mice, and that the main active substance of its extracts was identified as a polyterpene, Hypsiziprenol A_9. Hypsiziprenol A_9 inhibited the growth of various human cancer cell lines. However, its antitumor mechanism has not been studied in detail. To elucidate its mechanism, we examined Hypsiziprenol A_9-induced apoptosis in human promyelocytic leukemia HL-60 cells. Hypsiziprenol A_9 strongly inhibited the growth of HL-60 cells in a dose-dependent manner. Formation of apoptotic bodies was observed within 4 hr of Hypsiziprenol A_9 treatment. Pan-caspase inhibitor (Z-VAD-FMK) attenuated anti-proliferation effect of Hypsiziprenol A_9. Hypsiziprenol A_9-induced apoptosis was strongly inhibited by CAMP analogue (DBcAMP) or by CAMP-eleveting agents (Forskolin and IBMX), whereas p38 MAPK inhibitor (SB203580), JNK inhibitor (SP600125) and calcium chelators (EGTA, BAPTA-AM) had no effect. Thus, these results suggest that Hypsiziprenol A_9 inhibits the growth of HL-60 cells by inducing apoptosis via the down-modulation of CAMP signaling pathway.
