The mushroom Ganoderma lucidum, a lamellaless basidio-mycetous fungus belonging to the family Polyporaceae, is widely distributed in Korea, Japan and China, and has been used as a medicinal material for allergy, arthritis, bronchitis, gastric ulcer, hyperglycemia, hypertension, chronic hepatitis, hepatopathy, insomnia, nephritis, neurasthenia, scleroderma and inflammation. In addition, G. lucidum has been known to exert anti-cancer activities in many human cancer cells, but the cellular and molecular mechanism of this effect is poorly understood in human leukemia cells. In the present study, we investigated the pro-apoptotic effects of water extract of wild Ganoderma lucidum spores (WEGL) in human leukemia U937 cells. It was found that exposure of U937 cells to WEGL resulted in the growth inhibition in a dose-dependent manner as measured by trypan blue count and MTT assay. The anti-proliferative effect of WEGL 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 WEGL was connected with a up-regulation of pro-apoptotic Bax expression and down-regulation of X-linked inhibitor of apoptosis protein (XIAP). In addition, WEGL treatment inhibited the levels of pro-caspase-3 and a concomitant degradation of poly (ADP-ribose) polymerase (PARP). Taken together, the present results suggest that WEGL may be a potential chemotherapeutic agent for the control of human leukemia U937 cells and further studies will be needed to identify the active compounds. (Cancer Prev Res 15, 347-357, 2010)

Keywords: WEGL, U937, Apoptosis, Caspase-3