Inhibition of the tumor-promoting action of 12-O-tetradecanoylphorbol-13-acetate by some oleanane-type triterpenoid compounds.
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.
Nishino
H
H
Department of Biochemistry, Kyoto Prefectural University of Medicine, Japan.
Nishino
A
A
Takayasu
J
J
Hasegawa
T
T
Iwashima
A
A
Hirabayashi
K
K
Iwata
S
S
Shibata
S
S
D000818:Animals; D002478:Cells, Cultured; D006034:Glycyrrhetinic Acid / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D012878:Skin Neoplasms / Q000139:chemically induced; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors*; D014315:Triterpenes / Q000494:pharmacology*
D014315:Triterpenes; D013755:Tetradecanoylphorbol Acetate; D006034:Glycyrrhetinic Acid