Curcumin Reduces Mcp-1 Expression And Concentration In The ApcMin/+ Mouse

Numerous studies in rodent models argue for curcumin's chemopreventive potential in colon cancer. In fact we have recently shown that curcumin can reduce both polyp number and size in the ApcMin/+ mouse model of colon cancer. However, the exact mechanisms for its effects have yet to be elucidated. Compelling evidence has emerged in recent years for macrophages playing an important role in tumor cell invasion into surrounding normal tissues, proliferation and survival, and metastasis to local distant sites. MCP-1 has been identified as the most important chemokine for macrophage recruitment in several human cancers including colon cancer and has been associated with increased grade of the tumor. However, there is no data on the effects of curcumin on the MCP-1 response in the ApcMin/+ mouse. PURPOSE: To determine the effects of curcumin on MCP-1 expression and concentration in the ApcMin/+ mouse model of colon cancer. METHODS: Male and female ApcMin/+ mice were randomly assigned to either placebo or curcumin (n=10/group) treatment, C57BL/6 mice were used as a wildtype control. Mice were given a placebo or curcumin (2%) diet from 4-18 wks of age. Tissues were collected at 18 wks of age, and intestines were analyzed for expression and concentration of MCP-1 in the small intestine (sections 2 and 3) using PCR and ELISA, respectively. Plasma was analyzed for MCP-1 concentration using ELISA. Statistical analysis of MCP-1 was performed using a one-way ANOVA with Student-Newman-Keuls post hoc analysis (P≤0.05). RESULTS: Expression of MCP-1 was increased in intestinal sections 2 and 3 (P<0.05) and curcumin offset this effect (P<0.05). Concentration of MCP-1 was increased in intestinal sections 2 and 3 (P<0.05) and curcumin was effective in blunting this response in section 3 (P<0.05). Similarly, MCP-1 was increased in plasma (P<0.05) and curcumin offset this effect (P<0.05). CONCLUSIONS: These data suggest that curcumin can block the increased concentration and expression of MCP-1 in the ApcMin/+ mouse model of colon cancer. This may at least partly explain the benefits of curcumin on reducing polyp number and size in this model. Targeting MCP-1 using nutritional strategies such as curcumin may provide important therapeutic interventions in colon cancer.