title: A polysaccharide from the fruiting bodies of Agaricus blazei Murill induces caspase-dependent apoptosis in human leukemia HL-60 cells.
abstract: Polysaccharides are the major active ingredients of fungus Agaricus blazei for treating and preventing cancer. However, there are no reports showing anti-tumor activity of A. blazei polysaccharides (ABP) on human leukemia (HL)-60 cells in vitro and in vivo. In this study, we demonstrated that ABP efficiently inhibited proliferation of cultured HL-60 cells, which was associated with the induction of apoptosis. The increase in ABP-induced apoptosis was accompanied by loss of mitochondria membrane potential (∆Ψm), cytochrome c release from the mitochondria, activation of caspase-3, degradation of poly(ADP-ribose) polymerase (PARP), and the elevated ratio of Bcl-2-associated X (Bax)/B-cell lymphoma 2 (Bcl-2). Moreover, z-DEVD-fmk, a caspase-3 inhibitor, reversed the cytotoxic effects and apoptotic characteristics induced by ABP in HL-60 cells. Furthermore, we confirmed that ABP could obviously inhibit the solid cancer growth of leukemia HL-60 in tumor xenograft model. These data demonstrated that ABP effectively induced the apoptosis of HL-60 cells via a signaling cascade of mitochondrial caspase-3-dependent pathway.
authors.affiliation: The Center of Tumor Research and Therapy, Shandong Provincial Hospital to Shandong University, Jinan, 250021, Shandong Province, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Li
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.forename: Hongmin
authors.initials: H
authors.lastname: Wang
authors.forename: Junqing
authors.initials: J
authors.lastname: Han
authors.forename: Li
authors.initials: L
authors.lastname: Liu
mesh_terms: D000364:Agaricus / Q000737:chemistry*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D048690:Fruiting Bodies, Fungal / Q000737:chemistry*; D018922:HL-60 Cells; D019073:HT29 Cells; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008819:Mice, Nude; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011134:Polysaccharides / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D011134:Polysaccharides; D019253:Proto-Oncogene Proteins c-bcl-2; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D020169:Caspases