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, as estimated by gel permeation chromatography. The conditioned medium prepared with PC-PS (15 microg/ml)-stimulated human blood mononuclear cells for 5 days (PC-PS-MNC-CM5) 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.
Chen
Yue-Yawn
YY
Graduate Institute of Food Science and Technology, National Taiwan University, Taipei 106-17, Taiwan.
Chang
Hung-Min
HM
D015703:Antigens, CD; D000951:Antigens, Neoplasm / Q000096:biosynthesis; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004365:Drugs, Chinese Herbal / Q000737:chemistry*; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007938:Leukemia / Q000188:drug therapy; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects*; D009500:Neutralization Tests; D011134:Polysaccharides / Q000302:isolation & purification / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D020298:U937 Cells / Q000187:drug effects; D000070660:Wolfiporia
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000972:Antineoplastic Agents, Phytogenic; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D011134:Polysaccharides; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma