Antiproliferative and differentiating effects of polysaccharide fraction from fu-ling (Poria cocos) on human leukemic U937 and HL-60 cells

Poria cocos (PC), Fu-Ling, is an oriental fungus and has been widely used as a Chinese traditional herbal medicine for centuries. In the present study, a neutral polysaccharide fraction from PC (PC-PS) was isolated by a series of chromatographies and its effects on antiproliferation and differentiation of human leukemic cells, U937 and HL-60, were investigated in vitro. Results showed that the molecular weight of isolated PC-PS was approximately 160 kDa, Lis estimated by gel permeation chromatography. The conditioned medium Prepared with PC-PS (15 mug/ml)-stimulated human blood mononuclear cells for 5 days (PC-PS-MNC-CMS) exhibited a potent activity in suppressing the proliferation of U937 and HL-60 cells by 87.3 and 74.7%, respectively. Furthermore, PC-PS-MNC-CM5 induced about 66.6% of the U937 cells and 49.4% of the HL-60 cells to differentiate into mature monocytes/ macrophages, which also markedly expressed surface antigens of CD11b, CD14, and CD 68. The differentiated U937 and HL-60 cells displayed physiological functions such as respiratory burst and phagocytosis, while PC-PS group and control group showed insignificant effects. Interestingly, the levels of interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha in PC-PS-MNC-CM were about 41 and 10 times, respectively, higher than that of control group. Antibody neutralization tests of the PC-PS-MNC-CM5 revealed that the growth-inhibitory and differentiation-inducing activities were mainly due to the elevated cytokines of IFN-gamma and TNF-alpha. It suggests that PC-PS is a biological response modifier (BRM), instead of a cytotoxic reagent, and may be a potential alternative in leukemia therapy. (C) 2004 Published by Elsevier Ltd.