title: Cytotoxic activities and anti-tumor-promoting effects of microbial transformation products of prenylated chalcones from Angelica keiskei.
abstract: Three prenylated chalcones, 4-hydroxyderricin (1), xanthoangelol (2), and xanthoangelol F (3), isolated from Angelica keiskei, were transformed by the fungus Aspergillus saitoi. These chalcones were converted to flavanones (i.e., 4, 8, and 12), and prenyl-chain-hydrated (i.e., 5, 7, 9-11, and 13) and ring-B-hydroxylated (i.e., 6) chalcones. The structures of three new metabolites, 7, 9, and 13, were established as 2″,3″-dihydro-4,3″-dihydroxyderricin, 6″,7″-dihydro-7″-hydroxyxanthoangelol, and 6″,7″-dihydro-7″-hydroxyxanthoangelol F, respectively. Upon evaluation of cytotoxic activities of compounds 1-13, the metabolite 7 exhibited potent cytotoxicity against HL60 cells, and this cell death was revealed to be mostly due to apoptosis. In addition, compounds 1-4, 7-10, 12, and 13 were examined for their inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. All compounds tested showed inhibitory effects against EBV-EA activation with potencies higher than that of β-carotene. Furthermore, the metabolite 13 exhibited inhibitory effect on skin tumor promotion in an in vivo two-stage mouse skin carcinogenesis test based on 7,12-dimethylbenz[a]anthracene (DMBA) as initiator, and with TPA as promoter.
authors.affiliation: College of Science and Technology, Nihon University, 1-8-14 Kanda Surugadai, Chiyoda-ku, Tokyo 101-8308, Japan. akihisa.toshihiro@nihon-u.ac.jp
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Akihisa
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Motoi
authors.forename: Akihito
authors.initials: A
authors.lastname: Seki
authors.forename: Takashi
authors.initials: T
authors.lastname: Kikuchi
authors.forename: Makoto
authors.initials: M
authors.lastname: Fukatsu
authors.forename: Harukuni
authors.initials: H
authors.lastname: Tokuda
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Suzuki
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Kimura
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D029969:Angelica / Q000737:chemistry*; D000818:Animals; D000956:Antigens, Viral / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001230:Aspergillus / Q000187:drug effects / Q000254:growth & development; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D047188:Chalcones / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D054876:Prenylation; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: C572906:2'',3''-dihydro-4,3''-dihydroxyderricin; C572907:6'',7''-dihydro-7''-hydroxyxanthoangelol F; D000956:Antigens, Viral; D000972:Antineoplastic Agents, Phytogenic; D002273:Carcinogens; D047188:Chalcones; C033305:Epstein-Barr virus early antigen; D015127:9,10-Dimethyl-1,2-benzanthracene; D013755:Tetradecanoylphorbol Acetate