sarcophytol-a and Pancreatic-Neoplasms

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.

Topics: Animals; Antineoplastic Agents; Carcinogens; Cricetinae; Diterpenes; Female; Genes, ras; Mesocricetus; Mutation; Nitrosamines; Pancreatic Neoplasms; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; Proliferating Cell Nuclear Antigen

Sarcophytol A (SaA), a cembrane-type diterpene isolated from the marine soft coral Sarcophyton glaucum showed anticancer and cancer preventive effects in two different experiments. Growth of transplanted human pancreatic cancer cells (MIA paca-2, 1 x 10(7)) in nude mice (BALB/C 4W female) (Experiment 1) and pancreatic carcinogenesis induced by N-nitrobis-(2-hydroxypropyl) amine (BHP, 500 mg/kg) in Syrian golden hamsters (7W female) (Experiment 2) were inhibited by feeding the animals a diet containing 0.01% SaA. In Experiment 1, on day 29 after transplantation, tumor volume was significantly less in the SaA group than in the control group (1,759 + 310 mm3 vs. 2,364 + 467 mm3) (p < 0.05). In Experiment 2, the incidence of pancreatic tumors in the SaA group was 42.8% and that in the control group was 90.0% at 25-27 weeks. Thus, pancreatic carcinoma developed more slowly in the SaA group than in the control group. In addition, the incidence of atypical ductal hyperplasia and carcinoma in situ was lower in the SaA group. These results indicate that oral SaA administration is an effective vehicle for inhibition of certain types of cancer in hamsters.

Topics: Animals; Antineoplastic Agents; Carcinogens; Cricetinae; Disease Models, Animal; Diterpenes; Female; Mesocricetus; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Nitrosamines; Organ Size; Pancreatic Neoplasms; Tumor Cells, Cultured