Natural resin
acids present in
rosin of Pinus spez., including
isopimaric acid (1), mercusic
acid (2), neoabietic
acid (3),
dehydroabietic acid (4), and
podocarpic acid (8), as well
as resin acid derivatives 8β,9α,13α-H-tetrahydroabietic
acid (5), 8α,9α,13α-H-tetrahydroabietic
acid (6), 13α-H-Δ(8)-dihydroabietic
acid (7),
maleopimaric acid (9), and
fumaropimaric acid (10), were studied for their possible inhibitory effects on
Epstein-Barr virus early antigen (
EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Compounds 1, 3, 4, 7, and 10 (IC(50): 352, 330, 311, 340, and 349, respectively) exhibited strong inhibitory effects compared to the other compounds. Among these, 1, 4, and 7 were selected to examine their effects on in vivo two-stage mouse skin
carcinogenesis induced by 7,12-dimethylbenz[a]
anthracene (DMBA) as initiator and TPA as promoter. Treatment with compounds 4 and 7 (85 nmol) along with DMBA/TPA inhibited
papilloma formation up to week 8 and the percentage of
papilloma bearers in these two groups was approximately 80% at week 20. The average number of
papillomas formed per mouse was 4.4 and 4.2 even at week 20 (p>0.05). Compounds 4 and 7 exhibited high activity in the in vivo anti-
tumor-promoting test. In addition,
rosin was examined in vivo for its chemopreventive effect. Treatment with
rosin (50 μmol) along with DMBA (100 μg)/TPA (1 μg) inhibited
papilloma formation up to week 8 and the percentage of
papilloma bearers in this group was less than 80% at week 20. The average number of
papillomas formed per mouse in the
rosin-treated group was 3.8 even at week 20 (p>0.05). The in vivo two-stage mouse skin
carcinogenesis test revealed that
rosin possessed a pronounced anticarcinogenetic effect, and its high activity is due to the synergism of the
diterpenes contained in it.