title: Ganoderma atrum polysaccharide induces anti-tumor activity via the mitochondrial apoptotic pathway related to activation of host immune response.
abstract: Ganoderma atrum polysaccharide (PSG-1), the major active ingredient isolated from Ganoderma atrum, has been suggested as a candidate for cancer therapy. The aim of this study was to investigate the anti-tumor effect of PSG-1 using sarcoma 180 (S-180) transplanted mice and further to examine the molecular mechanisms of PSG-1-induced anti-tumor effect. Results showed that PSG-1 significantly inhibited tumor growth in S-180-bearing mice. PSG-1-induced tumor apoptosis was associated with the alteration of Bcl-2 family proteins, increase of reactive oxygen species generation, loss of mitochondrial membrane potential (Δψ(m) ), release of cytochrome c from the mitochondria into cytosol, and activation of caspase-3 and -9. Elevation of immune function was also shown during PSG-1-induced tumor apoptosis, as evidenced by increase of spleen and thymus indexes, lymphocyte proliferation, concentrations of tumor necrosis factor (TNF)-α, and interleukin-2 in serum. Furthermore, the combined treatment of PSG-1 and cyclophosphamide (CTX) results in an enhancement of the anti-tumor effect of CTX alone via increased host immune response. These results suggested that PSG-1 had a potent anti-tumor activity by induction of tumor apoptosis through mitochondrial pathways, and immunoenhancement effect of PSG-1 was related to its anti-tumor effect. In addition, PSG-1 enhanced CTX-induced anti-tumor activity in S-180-bearing mice.
authors.affiliation: State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China.
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.forename: Shao-Ping
authors.initials: SP
authors.lastname: Nie
authors.forename: Ming-Yong
authors.initials: MY
authors.lastname: Xie
authors.forename: Ming
authors.initials: M
authors.lastname: He
authors.forename: Shen-Shen
authors.initials: SS
authors.lastname: Zhang
authors.forename: Ke-Xue
authors.initials: KX
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003520:Cyclophosphamide / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D004357:Drug Synergism; D004789:Enzyme Activation; D032902:Ganoderma / Q000737:chemistry*; D008214:Lymphocytes / Q000166:cytology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D009368:Neoplasm Transplantation; D011134:Polysaccharides / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D014183:Transplantation, Heterologous; D047368:Tumor Burden / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C494827:Bax protein, mouse; D016207:Cytokines; D011134:Polysaccharides; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C052617:Bcl2 protein, mouse; D003520:Cyclophosphamide; D045304:Cytochromes c; D053148:Caspase 3; D053453:Caspase 9