title: AKT signalling and mitochondrial pathways are involved in mushroom polysaccharide-induced apoptosis and G1 or S phase arrest in human hepatoma cells.
abstract: This study describes molecular mechanisms for inhibiting tumour cell proliferation using polysaccharides from medicinal mushrooms in human hepatoma cells. The results show that regarding cell cycle-related proteins, three types of polysaccharides significantly enhance the expression of p27(Kip) in HepG2 and Bel-7404 cells, while suppressing the activity of cyclin D1/CDK4 and/or cyclin E/CDK2. Considering apoptosis-related factors, the polysaccharides suppressed AKT activity through the inhibition of AKT phosphorylation at Thr(308) and/or Ser(473). The growth of HepG2 and Bel-7404 cells was suppressed by the up-regulation of a subunit of PI3K and phospho-PTEN, which are modulators of AKT activity. The polysaccharides also activated the mitochondria-mediated apoptosis pathway by stimulating the activation of Bcl-2 family proteins to release cytochrome c and Smac and cleave caspase-9 and caspase-3 in HepG2 and Bel-7404 cells. These factors have a potent effect on cell cycle arrest in G(1) and/or S phase and induce apoptosis in HepG2 and Bel-7404 cells.
authors.affiliation: College of Life Sciences, Northeast Forestry University, Harbin 150040, PR China.
authors.forename: Fengju
authors.initials: F
authors.lastname: OuYang
authors.forename: Guibin
authors.initials: G
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Wenhua
authors.initials: W
authors.lastname: Xiang
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
mesh_terms: D000363:Agaricales / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects; D001685:Biological Factors / Q000302:isolation & purification / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D011134:Polysaccharides / Q000302:isolation & purification / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D001685:Biological Factors; D018797:Cell Cycle Proteins; D011134:Polysaccharides; D051057:Proto-Oncogene Proteins c-akt