title: Antileukemia component, dehydroeburicoic acid from Antrodia camphorata induces DNA damage and apoptosis in vitro and in vivo models.
abstract: Antrodia camphorata (AC) is a native Taiwanese mushroom which is used in Asian folk medicine as a chemopreventive agent. The triterpenoid-rich fraction (FEA) was obtained from the ethanolic extract of AC and characterized by high performance liquid chromatography (HPLC). FEA caused DNA damage in leukemia HL 60 cells which was characterized by phosphorylation of H2A.X and Chk2. It also exhibited apoptotic effect which was correlated to the enhancement of PARP cleavage and to the activation of caspase 3. Five major triterpenoids, antcin K (1), antcin C (2), zhankuic acid C (3), zhankuic acid A (4), and dehydroeburicoic acid (5) were isolated from FEA. The cytotoxicity of FEA major components (1-5) was investigated showing that dehydroeburicoic acid (DeEA) was the most potent cytotoxic component. DeEA activated DNA damage and apoptosis biomarkers similar to FEA and also inhibited topoisomerase II. In HL 60 cells xenograft animal model, DeEA treatment resulted in a marked decrease of tumor weight and size without any significant decrease in mice body weights. Taken together, our results provided the first evidence that pure AC component inhibited tumor growth in vivo model backing the traditional anticancer use of AC in Asian countries.
authors.affiliation: Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
authors.forename: Ying-Chi
authors.initials: YC
authors.lastname: Du
authors.forename: Fang-Rong
authors.initials: FR
authors.lastname: Chang
authors.forename: Tung-Ying
authors.initials: TY
authors.lastname: Wu
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Hsu
authors.forename: Mohamed
authors.initials: M
authors.lastname: El-Shazly
authors.forename: Chieh-Fu
authors.initials: CF
authors.lastname: Chen
authors.forename: Ping-Jyun
authors.initials: PJ
authors.lastname: Sung
authors.forename: Yan-Yu
authors.initials: YY
authors.lastname: Lin
authors.forename: Yi-Hsin
authors.initials: YH
authors.lastname: Lin
authors.forename: Yang-Chang
authors.initials: YC
authors.lastname: Wu
authors.forename: Mei-Chin
authors.initials: MC
authors.lastname: Lu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D055491:Antrodia / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects; D064447:Checkpoint Kinase 2; D002851:Chromatography, High Pressure Liquid; D004249:DNA Damage / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D004875:Ergosterol / Q000031:analogs & derivatives / Q000302:isolation & purification; D005260:Female; D018922:HL-60 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D007810:Lanosterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D007938:Leukemia / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008516:Medicine, Chinese Traditional; D051379:Mice; D008819:Mice, Nude; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D059005:Topoisomerase II Inhibitors / Q000737:chemistry / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C468783:H2AX protein, human; D006657:Histones; D059005:Topoisomerase II Inhibitors; C547186:dehydroeburicoic acid; C098367:zhankuic acid A; C098428:zhankuic acid C; D007810:Lanosterol; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; C578633:Chek2 protein, mouse; D017346:Protein Serine-Threonine Kinases; D004875:Ergosterol