Sarcophytol A (SaA), a
cembrane-type
diterpene, inhibits pancreatic
carcinogenesis induced by
N-nitrosobis(2-oxypropyl)amine (BOP) in hamsters. The experimental groups received two
injections of BOP at 70 mg/kg dose, followed 2 weeks later by a 20 mg/kg dose injection, and were fed a basal diet or 0.01 and 0.05% SaA diets starting 1 week after the second injection of BOP. Control groups were injected with
normal saline and fed the basal diet or the 0.05% SaA diet. All animals were killed 30 weeks after the start of the experiments. Seventeen BOP-treated hamsters fed the basal diet developed pancreatic
tumors (77.3%) while only 12 of 21 hamsters fed the 0.01% SaA diet (57.1%) and 12 of 23 hamsters fed the 0.05% SaA diet (52.2%) developed pancreatic
tumors. Pancreatic lesions included
ductal hyperplasia, atypical ductal
hyperplasia, and
carcinoma in situ. Microscopic invasive
carcinoma induced by BOP and the incidence of larger pancreatic
tumors in hamsters were significantly higher in hamsters fed the basal diet than in hamsters fed the SaA diet (p < 0.05). The
proliferating cell nuclear antigen (
PCNA) labeling index of
pancreatic carcinoma in BOP-treated hamsters fed the basal diet was 41.2 +/- 13.4%, whereas BOP-treated hamsters fed 0.01 and 0.05% SaA diets yielded
PCNA indexes of 26.8 +/- 8.3 and 28.4 +/- 7.0%, respectively. k-ras mutation was detected in 40% of
cancers in both groups. No pancreatic
tumors developed in saline-treated groups, and no differences in
body weights or histological findings in their organs, including the pancreas, were observed in either group. These findings suggest that SaA not only inhibits BOP-induced pancreatic
carcinogenesis in hamsters, but also provides antipromotion and antiprogression effects on these
tumors, even when SaA commences 1 week after the initiation of pancreatic
carcinogenesis.