Submitted to: International Journal of Cancer
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 30, 2012
Publication Date: June 22, 2012
Repository URL: http://handle.nal.usda.gov/10113/56800
Citation: Yan, L. 2012. Dietary supplementation with curcumin enhances metastatic growth of Lewis lung carcinoma in mice. International Journal of Cancer. doi: 10.1002/ijc.27683. Interpretive Summary: The present study investigated the effects of dietary supplementation with curcumin ((1E, 6E)-1,7-bis (4-hydroxy-3-methoxyphenyl) -1,6-heptadiene-3,5-dione) on spontaneous metastasis of Lewis lung carcinoma (LLC) cells in C57/BL6 mice. Mice were fed the AIN93G control diet or that diet supplemented with 2% or 4% curcumin for 5 weeks at which time they were injected subcutaneously with 2.5 x 105 viable LLC cells. The subcutaneous primary tumor was surgically removed when it reached approximately 8 mm in diameter, and the experiment was terminated 10 days after the surgery. There was no difference in pulmonary metastatic yield among the treatment groups. Curcumin supplementation at either dose level did not significantly affect tumor growth; however, the combine data from both curcumin groups showed that curcumin treatment increased tumor cross-sectional area by 46% (p < 0.05) and tumor volume by 70% (p < 0.05) compared with the controls. Curcumin supplementation also increased plasma concentrations of the angiogenic factors fibroblast growth factor-basic (p < 0.05) and vascular endothelial growth factor (p < 0.05), as well as the inflammatory cytokines interleukin-1ß (p < 0.05) and monocyte chemotactic protein-1 (p < 0.05) compared with the controls. These results demonstrate that curcumin does not prevent metastasis, and indicate that it can enhance metastatic growth of LLC in mice, perhaps through up-regulation of angiogenesis and inflammation.
Technical Abstract: Curcumin is a phenolic compound derived from the Curcuma longa plant, commonly known as turmeric. Curcumin has been used traditionally in Ayurvedic medicine as it has therapeutic properties including being anti-inflammatory, anti-oxidant and anti-microbial. The present study investigated the effects of dietary supplementation of curcumin on secondary cancer prevention. The secondary cancer prevention refers to the prevention of malignant spread from a primary tumor to distant organs, which is the most devastating aspect of cancer, and its occurrence directly affects the prognosis and survival of cancer patients. Results from the present study showed that dietary supplementation with 2% or 4% curcumin did not inhibit spread of cancer cells in laboratory rodents, but enhanced the growth of metastatic tumors developed in the lungs. Curcumin supplementation also increased plasma concentrations of angiogenic factors and inflammatory cytokines, indicating that curcumin may stimulate metastatic growth by up-regulating angiogenesis and inflammation. Angiogenesis, the formation of new blood vessels, is common in many malignancies in human patients, including breast, prostate and colorectal cancer. Therefore, it is possible that curcumin may play a role in the development of malignancies with rapid progression, including cancer recurrence and metastasis. This hypothesis warrants further investigation.