title: Induction of apoptosis in human hepatoma cells by mycelia of Antrodia camphorata in submerged culture.
abstract: The effect of methanolic extracts of mycelia (MEM) from Antrodia camphorata (Polyporaceac, Aphyllophorales) of submerged culture (ACSC) on the inhibition of cell viability and the mechanism of MEM-induced cytotoxic in hepatoma cells were investigated. The IC(50) of MEM on the cytotoxicity of HepG2 (wild type p53) and Hep3B (delete p53) were 49.5 and 62.7 microg/ml, respectively, on 48 h incubation. There is no observable cytotoxicity of MEM in Chang liver cells and rat primary hepatocytes at the concentration of 100 microg/ml. Cell cycle analysis revealed that MEM induced apoptosis on HepG2 via G0/G1 cell cycle arrest. MEM (100 microg/ml) treated HepG2 and Hep3B for 72 h, the apoptotic cells were 98.3 and 39.5%, respectively. The activities of caspase-3, -8 and -9 in HepG2 induced by MEM (50 microg/ml) were increased 5.3, 6.7 and 2.2-fold, respectively. MEM-induced apoptotic cell death was accompanied by up-regulation of caspase-3 and -8 in HepG2 cells. Combined treatment with MEM and caspase-3, -8 and -9 inhibitors, the caspase-3 and -8 inhibitors were accounting for 63 and 47% inhibition in MEM-induced apoptosis, respectively; however, caspase-9 inhibitor exhibited no obvious inhibition effect on the apoptosis percentage (p>0.05). The results indicated that MEM induced HepG2 apoptosis through activation of caspase-3 and -8 cascades and regulation of the cell cycle progression to inhibit hepatoma cells proliferation.
authors.affiliation: Department of Food Science, National Chung Hsing University, 250 Kuokuang Road, Taichung 40227, Taiwan.
authors.forename: Tuzz-Ying
authors.initials: TY
authors.lastname: Song
authors.forename: Shih-Lan
authors.initials: SL
authors.lastname: Hsu
authors.forename: Gow-Chin
authors.initials: GC
authors.lastname: Yen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001487:Basidiomycota / Q000737:chemistry*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D051381:Rats
chemical_list: D000970:Antineoplastic Agents; D061945:Caspase Inhibitors; D020169:Caspases