Inhibition of the tumor-promoting action of 12-O-tetradecanoylphorbol-13-acetate by some oleanane-type triterpenoid compounds

Cancer Res. 1988 Sep 15;48(18):5210-5.

Abstract

Since glycyrrhetinic acid was proved to suppress tumor promoter effects, several oleanane-type triterpenes which were chemically derived from oleanolic acid and hederagenin were tested in vitro and in vivo against the action of tumor promoter, 12-O-tetradecanoylphorbol 13-acetate. By in vitro experiment monitoring with 12-O-tetradecanoylphorbol-13-acetate-induced stimulation of 32Pi incorporation into phospholipids and an in vivo test on skin tumor formation in mice initiated with 7,12-dimethylbenz[a]anthracene and promoted with 12-O-tetradecanoylphorbol-13-acetate, 18 beta-olean-12-ene-3 beta,28-diol (= erythrodiol), 18 beta-olean-12-ene-3 beta,23,28-triol, 18 alpha-olean-12-ene-3 beta,28-diol, and 18 alpha-olean-12-ene-3 beta,23,28-triol showed remarkable suppressive effects. Especially 18 alpha-oleanane derivatives having a CH2OH grouping converted from the COOH group initially allocated at C-17 were 100 times more effective than glycyrrhetinic acid both in vitro and in vivo.

MeSH terms

  • Animals
  • Cells, Cultured
  • Glycyrrhetinic Acid / pharmacology
  • Mice
  • Mice, Inbred C3H
  • Skin Neoplasms / chemically induced
  • Structure-Activity Relationship
  • Tetradecanoylphorbol Acetate / antagonists & inhibitors*
  • Triterpenes / pharmacology*

Substances

  • Triterpenes
  • Tetradecanoylphorbol Acetate
  • Glycyrrhetinic Acid