Agaricus blazei Murill is a traditional herb medicine which has been used for patient suffering from cancer in Oriental medicine. It used to be a source of antitumor and immunoactive compounds in Oriental medicine, and considered a health food in many countries. In the present study, it was examined the biochemical mechanisms of apoptosis by water extract of Agaricus blazei Murill (WEAB) in human leukemia U937 cells. It was found that WEAB could inhibit the cell growth of U937 cells in a dose-dependent manner, which was associated with apoptotic cell death such as formation of apoptotic bodies and DNA fragmentation. Flow cytometry analysis confirmed that WEAB treatment increased populations of apoptotic-sub G1 phase. Apoptosis of U937 cells by WEAB was associated with a down-regulation of anti-apoptotic Bcl-2 expression and an up-regulation of pro-apoptotic Bax expression. WEAB treatment induced the proteolitic activation of caspase-3, 8, 9 and downregulation of pAkt or upregulation of pERK. These results indicated that the anti-proliferative effects of WEAB were associated with the induction of apoptotic cell death through regulation of several major growth regulatory gene products such as Bcl-2 family expression and caspase protease ativity though activation of pERK or inactivation of pAkt, and WEAB may have therapeutic potential in human leukemia treatment. (Cancer Prev Res 12, 98-105, 2007)

Keywords: Agaricus blazei Murill, Apoptosis, Bcl-2, Bax, Caspase