Cordyceps militaris produces several bioactive ingredients and exhibits medicinal effects as a traditional Chinese medicine. Cordycepin (3'-deoxyadenosine) is one of the major bioactive substances produced by C. militaris and possesses several biological activities, including both pro-apoptotic and anti-apoptotic properties. In order to develop new variety varieties which have large amounts of cordycepin, we previously produced a novel improved race between two fungal strains (MPNU10306 and MPNU10366) formerly known as C. militaris. In the present report, we compared the pro-apoptotic effects of the water extracts of two parent strains (CMA and CMB) and mating type (CMAB) in U937 human leukemic cells. It was found that exposure of U937 cells to CMAB resulted in the growth inhibition in a dose-dependent, whereas the inhibition effects appeared weakly in CMA and CMB-treated U937 cells. The anti-proliferative effect of CMAB treatment in U937 cells was associated with apoptotic cell death such as increased populations of apoptotic-sub G1 phase, formation of apoptotic bodies, DNA fragmentation and increased the percentage of cells with depolized mitochondrial membrane. The induction of apoptotic cell death by CMAB was connected with an up-regulation of pro-apoptotic Bax expression and down-regulation of anti-apoptotic Bcl-2 and inhibitor of apoptosis (IAP) family proteins. In addition, CMAB treatment induced the proteolytic activation of caspases and cleavage of poly(ADP-ribose) polymerase and Ղ-catenin proteins. Taken together, the present results suggest that CMAB may be a potential chemotherapeutic agent for the control of human leukemia U937 cells. (Cancer Prev Res 17, 0-314, 2012)

Keywords: Cordyceps militaris, U937, Apoptosis, Caspase