title: Ganoderic acid X, a lanostanoid triterpene, inhibits topoisomerases and induces apoptosis of cancer cells.
abstract: Lanostanoid triterpenes isolated from Ganoderma amboinense were found to inhibit the growth of numerous cancer cell lines, and some of them inhibited the activities of topoisomerases I and IIalpha in vitro. Among the bioactive isolates, one of the most potent triterpene was identified to be 3 alpha-hydroxy-15 alpha-acetoxy-lanosta-7,9(11),24-trien-26-oic acid, ganoderic acid X (GAX). Treatment of human hepatoma HuH-7 cells with GAX caused immediate inhibition of DNA synthesis as well as activation of ERK and JNK mitogen-activated protein kinases, and cell apoptosis. Molecular events of apoptosis including degradation of chromosomal DNA, decrease in the level of Bcl-xL, the disruption of mitochondrial membrane, cytosolic release of cytochrome c and activation of caspase-3 were elucidated. The ability of GAX to inhibit topoisomerases and to sensitize the cancer cells toward apoptosis fulfills the feature of a potential anticancer drug.
authors.affiliation: Graduate Institute of Medical Technology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.
authors.forename: Chyi-Hann
authors.initials: CH
authors.lastname: Li
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Chen
authors.forename: Ue-Min
authors.initials: UM
authors.lastname: Chang
authors.forename: Lou-Sing
authors.initials: LS
authors.lastname: Kan
authors.forename: Woei-Horng
authors.initials: WH
authors.lastname: Fang
authors.forename: Keh-Sung
authors.initials: KS
authors.lastname: Tsai
authors.forename: Shwu-Bin
authors.initials: SB
authors.lastname: Lin
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D032902:Ganoderma / Q000737:chemistry; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007810:Lanosterol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D008516:Medicine, Chinese Traditional; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D014315:Triterpenes / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use
chemical_list: C501828:3alpha-hydroxy-15alpha-acetoxy-lanosta-7,9(11),24-trien-26-oic acid; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D014315:Triterpenes; D007810:Lanosterol; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II