Potential anti-tumor promoting activity of lupane-type triterpenoids from the stem bark of Glochidion zeylanicum and Phyllanthus flexuosus.
Four known lupane-type triterpenoids, glochidonol (1), glochidiol (2), lup-20(29)-ene-1beta,3beta-diol (3) and glochidone (3) were isolated from the stem bark of Glochidion zeylanicum. Previously, lupeol (5), lup-20(29)-ene-3beta,24-diol (6) and betulin (7) were isolated from the stem bark of Phyllanthus flexuosus. This study reports the assays of these lupane-type triterpenoids: all isolates 1-7 and synthetic analogues, glochidonyl acetate (1a), lup-20(29)-ene-1,3-dione (1b) and lup-20(29)-ene 3beta,24-diacetate (6a) were tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol 13-acetate (TPA). Among them, the effects of compounds 2 (IC50 = 290 mol ratio/32 pmol TPA) and 3 (IC50 = 300) were stronger than the others. In addition, compound 2 exhibited a strong inhibitory effect on mouse skin tumor promotion in an in vivo mouse two-stage carcinogenesis test.
Tanaka
Reiko
R
Department of Medicinal Chemistry, Osaka University of Pharmaceutical Sciences, Osaka, Japan. tanakar@gly.oups.ac.jp
Kinouchi
Yoshitaka
Y
Wada
Shun-ichi
S
Tokuda
Harukuni
H
D015127:9,10-Dimethyl-1,2-benzanthracene; D000279:Administration, Cutaneous; D000818:Animals; D000956:Antigens, Viral / Q000187:drug effects; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D004854:Herpesvirus 4, Human / Q000187:drug effects / Q000276:immunology; D020128:Inhibitory Concentration 50; D051379:Mice; D008813:Mice, Inbred ICR; D010212:Papilloma / Q000139:chemically induced / Q000517:prevention & control; D029803:Phyllanthus; D008517:Phytotherapy; D024301:Plant Bark; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control; D013047:Specific Pathogen-Free Organisms; D013755:Tetradecanoylphorbol Acetate; D014315:Triterpenes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D053978:Pentacyclic Triterpenes
D015127:9,10-Dimethyl-1,2-benzanthracene; D000956:Antigens, Viral; D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D013755:Tetradecanoylphorbol Acetate; D014315:Triterpenes; C480546:lupane; D053978:Pentacyclic Triterpenes