Chemopreventive Effects of 4-Methylthio-3-butenyl Isothiocyanate (Raphasatin) but Not Curcumin against Pancreatic Carcinogenesis in Hamsters

The modifying effects of 4-methylthio-3-butenyl isothiocyanate (MTBITC) and curcumin were investigated in N-nitrosobis(2-oxopropyl)amine (BOP)-initiated hamsters. Male 6-week-old Syrian hamsters were subcutaneously injected with 10 mg/kg body weight (b.w.) of BOP four times a week, and fed a diet supplemented with 80 mg/kg diet of MTBITC, equivalent to 4.6 mg/kg b.w./day for the initiation stage or 3.8 mg/kg b.w./day for the postinitiation stage administration, respectively, or 2000 mg/kg diet of curcumin, equivalent to 118.8 mg/kg b.w./day for the initiation stage or 100.8 mg/kg b.w./day for the postinitiation stage administration, respectively. The incidence of combined pancreatic lesions, including atypical hyperplasias and adenocarcinomas, was significantly decreased to 55% (P < 0.05) by the 80 mg/kg diet MTBITC given during the initiation stage as compared to the BOP alone group (85%) but not by the curcumin administration at 16 weeks after the BOP-treatment. In the second study, the multiplicity of combined pancreatic lesions was also significantly decreased to 0.50 ± 0.51 (P < 0.05) by 700 mg/kg diet MTBITC given in the initiation stage (equivalent to 59.0 mg/kg b.w./day) as compared to the BOP alone group (1.10 ± 1.02). Our results indicate that the naturally occurring isothiocyanate MTBITC may exert preventive effects against BOP-initiation of hamster pancreatic carcinogenesis.