Chemopreventive Effect of Curcumin on N‐Nitrosomethylbenzylamine‐induced Esophageal Carcinogenesis in Rats

Modifying effects of curcumin (derived from the rhizome of Curcuma longa L.) during the initiation or post‐initiation phase of N‐nitrosomethylbenzylamine (NMBA)‐induced esophageal carcinogenesis were investigated in male F344 rats. Five‐week‐old rats were divided into 5 groups, and groups 1, 2 and 3 were given intraperitoneal injections of NMBA (0.5 mg/kg body weight/injection 15 times) for 5 weeks from 7 weeks old to induce esophageal neoplasms. Groups 2 and 3 were fed the diet containing 500 ppm curcumin during the initiation and post‐initiation phases, respectively. Group 4 was given the diet containing curcumin throughout the experiment, and group 5 was kept on the basal diet alone and served as an untreated control. Incidence and multiplicity of esophageal neoplasms of group 1 (NMBA alone) were 66.7% and 0.83 ±0.70, respectively. Those of groups 2 and 3 were significantly less than those of group 1 (39.3%, 0.46±0.64, P < 0.05; 33.3%, 0.36±0.56, P < 0.05, respectively). Furthermore, the incidence and multiplicity of esophageal preneoplastic lesions (moderate or severe epithelial dysplasia) of group 2 (57.1%, 0.61±0.57; 40%, 0.29±0.46) or 3 (56.7%, 0.67±0.66; 23.3%, 0.23±0.43) were less than those of group 1 (100%, 1.67±0.70; 70.8%, 0.92±0.72) (P < 0.05). In this experiment, feeding of curcumin significantly decreased the expression of cell proliferation biomarkers (5‐bromo‐2′‐deoxyuridine labeling index) in the non‐lesional esophageal epithelium (P < 0.01). These findings indicate that curcumin inhibits NMBA‐induced esophageal carcinogenesis when given during the post initiation as well as initiation phase. This inhibition may be related to suppression of the increased cell proliferation induced by NMBA in the esophageal epithelium.