4-Methylthio-3-butenyl isothiocyanate (raphasatin) exerts chemopreventive effects against esophageal carcinogenesis in rats

To examine the effects of 4-methylthio-3-butenyl isothiocyanate on esophageal carcinogenesis, male 6-week-old F344 rats were subcutaneously injected with 0.5 mg/kg body weight N-nitrosomethylbenzylamine three times per week for 5 weeks and fed a diet supplemented with 80 ppm 4-methylthio-3-butenyl isothiocyanate, equivalent to 6.05 mg/kg body weight/day for the initiation stage, 4.03 mg/kg body weight/day for the promotion stage, or 4.79 mg/kg body weight/day for all stages. Although the incidence of lesions was not affected by 4-methylthio-3-butenyl isothiocyanate treatment, the multiplicity of squamous cell papilloma in the esophagus was significantly decreased in rats in the 4-methylthio-3-butenyl isothiocyanate initiation stage group (1.13 ± 0.74), 4-methylthio-3-butenyl isothiocyanate promotion stage group (1.47 ± 0.99), and 4-methylthio-3-butenyl isothiocyanate all stage group (1.47 ± 1.13) as compared with rats treated with N-nitrosomethylbenzylamine alone (3.00 ± 1.46). Immunohistochemical analysis revealed that 4-methylthio-3-butenyl isothiocyanate induced apoptosis, suppressed cell proliferation, and increased p21 expression when administered in the promotion phase. These modifying effects were not observed in the rats treated with 4-methylthio-3-butenyl isothiocyanate alone. Our results indicated that 4-methylthio-3-butenyl isothiocyanate may exert chemopreventive effects against N-nitrosomethylbenzylamine-induced esophageal carcinogenesis in rats.