Potential Anti-Tumor Promoting Activity of Lupane-Type Triterpenoids from the Stem Bark of Glochidion zeylanicum and Phyllanthus flexuosus

Abstract

Four known lupane-type triterpenoids, glochidonol (1), glochidiol (2), lup-20(29)-ene-1β,3β-diol (3) and glochidone (3) were isolated from the stem bark of Glochidion zeylanicum. Previously, lupeol (5), lup-20(29)-ene-3β,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 3β,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.

References

• 1 Matsunaga S, Tanaka R, Takaoka Y, In Y, Ishida T, Rarmani M, Ismail H BM. 26- nor-D: A-friedooleanane triterpenes from Phyllanthus watosonii .  Phytochemistry. 1993;  32 165-70
• 2 Tanaka R, Matsunaga S. Triterpene dienols and other constituents from the bark of Phyllanthus flexuosus .  Phytochemistry. 1988;  27 2273-7
• 3 Hui W H, Lee W K, Ng K K, Chan C K. The occurrence of triterpenoids and steroids in three Glochidion species.  Phytochemistry. 1970;  9 1099-102
• 4 Tanaka R, Tabuse M, Matsunaga S. Triterpenes from the stem bark of Phyllanthus flexuosus .  Phytochemistry. 1988;  27 3563-7
• 5 Tanaka R, Matsunaga S, Ishida T. Revised structure of trichadenic acid B, a stem bark constituent of Phyllanthus flexuosus .  Tetrahedron Letters. 1988;  29 4751-4
• 6 Huang M -T, Smart R. C, Wong C-Q, Conney A. H. Inhibition effect of curcumin, chlorogenic acid, caffeic acid, and ferulic acid on tumor promotion in mouse skin by 12-O-tetradecanoylphorbol 13-acetate.  Cancer Research. 1988;  48 5941-6
• 7 Ito Y, Kawanishi M, Harayama T, Takabayashi S. Combined effect of the extracts from Croton tiglium, Euphorbia lathyris or Euphorbia tirucalli and n-butyrate on Epstein-Barr virus expression in human lymphoblastoid P3HR-1 and Raji cells.  Cancer Letters. 1981;  12 175-80
• 8 Tokuda H, Ohigashi H, Koshimizu K, Ito Y. Inhibitory effects of ursolic acid and oleanolic acid on skin tumor promotion 12-O-tetradecanoylphorbol-13-acetate.  Cancer Letters. 1986;  33 279-85