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

Abstract

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.

Curcumin induces apoptosis-independent death in oesophageal cancer cells

“…Curcumin has shown potential as both a chemopreventive agent and a chemotherapeutic agent in various gastrointestinal cancers, and initial studies in oesophageal cancer have been encouraging (Ushida et al, 2000). In this study, we have investigated the effects of curcumin on panel of genetically and phenotypically heterogeneous oesophageal cancer cell lines.…”

Curcumin as “Curecumin”: From kitchen to clinic

“…Curcumin has also shown an ability to inhibit the mammary tumor-initiating activity of DMBA [110] and the in vivo formation of mammary DMBA-DNA adducts in female rats [111] and to exert chemopreventive activity when administered during the promotion/progression stage of colon carcinogenesis [91]. Meanwhile, one group has studied not only curcumin's chemopreventive effects but also its effects on the initiation or post-initiation phase of N-nitrosomethylbenzylamine (NMBA)-induced esophageal carcinogenesis in male F344 rats [100]. Using a slightly different approach, …”

Curcumin, a Dietary Component, Has Anticancer, Chemosensitization, and Radiosensitization Effects by Down-regulating the MDM2 Oncogene through the PI3K/mTOR/ETS2 Pathway

“…In rodent model systems, curcumin, a dietary component, inhibits the formation of carcinogen-induced cancers of the colon (39), oral cavity (40), forestomach (41), esophagus (42), stomach (43), lung (44), liver (45), and skin (46). In a small clinical study, p.o.…”