Ganoderiol F, a ganoderma triterpene, induces senescence in hepatoma HepG2 cells.
Ganoderiol F (GolF), a tetracyclic triterpene, was isolated from Ganoderma amboinense and found to induce senescence of cancer cell lines. GolF induced growth arrest of cancer cell lines HepG2, Huh7 and K562, but exerted much less effect in hepatoma Hep3B cells and normal lung fibroblast MRC5 cells, and no effect on peripheral blood mononuclear cells. GolF treatment of the cancer cells, with the exception of Hep3B, resulted in prompt inhibition of DNA synthesis and arrest of cell progression cycle in G1 phase. Short-term exposure of HepG2 cells to GolF temporarily arrested progression of the cell cycle; cell growth was recovered if the drug was withdrawn from the medium after a 24-h exposure. After 18 days of continuous treatment of HepG2 cells with 30 muM GolF, over 50% of cells were found to be enlarged and flattened, and were beta-galactosidase positive phenotypes of senescent cells. GolF was found to inhibit activity of topoisomerases in vitro, which may contribute to the inhibition of cellular DNA synthesis. Activation of the mitogen-activated protein kinase EKR and up-regulation of cyclin-dependent kinase inhibitor p16 were found in early stages of GolF treatment and were presumed to cause cell-cycle arrest and trigger premature senescence of HepG2 cells. The growth-arrest and senescence induction capability on cancer cells suggest anticancer potential of GolF.
Chang
Ue-Min
UM
Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, Taiwan ROC.
Li
Chyi-Hann
CH
Lin
Liang-In
LI
Huang
Cheng-Po
CP
Kan
Lou-Sing
LS
Lin
Shwu-Bin
SB
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects; D032902:Ganoderma / Q000737:chemistry*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014315:Triterpenes / Q000494:pharmacology*; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis
D000903:Antibiotics, Antineoplastic; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; D014315:Triterpenes; D025521:Tumor Suppressor Proteins; C513307:ganoderiol F; D020928:Mitogen-Activated Protein Kinases; D004264:DNA Topoisomerases, Type I