Donna Zhang, Ph.D.; Georg Wondrak, Ph.D.
University of Arizona
NIEHS Grants P30ES006694, T32ES007091, R01ES015010
Researchers, funded in part by NIEHS, showed that adding a compound found in cinnamon to the diet of mice protected against colorectal cancer. They also revealed new information about the role that the nuclear factor-E2-related factor 2 (Nrf2) plays in the compound’s protective effects.
The Nrf2 molecular pathway is a master regulator of the cellular antioxidant defense, and thus plays a key role in protecting cells against stressors, such as carcinogen exposure and environmental damage. Cinnamon is a rich dietary source of cinnamaldehyde, which brings about an Nrf2-regulated antioxidant response in human epithelial colon cells.
In the new study, the researchers first used human colon epithelial cells to better understand the molecular mechanisms involved in Nrf2 activation. They found that cinnamaldehyde-induced Nrf2 activation was largely dependent on Kelch-like ECH-associated protein 1 (Keap1)-Cys151 status. Keap -1 is a stabilizer of Nrf2 that, together with other molecules, promotes antioxidant pathways. They also compared the protective potential of the compound in a mouse colorectal cancer model with Nrf2 and without Nrf2. When the mice received cinnamaldehyde supplementation, only those expressing Nrf2 showed colorectal cancer suppression, providing evidence that cinnamaldehyde’s protective effects depend on Nrf2.
Together, the new findings suggest that cinnamaldehyde, an FDA-approved food additive, may be a feasible way to suppress colorectal cancer. However, the researchers say that more studies are needed to determine the cinnamaldehyde dose needed for Nrf2 activation and to test the feasibility of using cinnamon powder as a source of cinnamaldehyde for dietary cancer prevention.
Citation: Long M, Tao S, Rojo de la Vega M, Jiang T, Wen Q, Park SL, Zhang DD, Wondrak GT. 2015. Nrf2-dependent suppression of azoxymethane/dextran sulfate sodium-induced colon carcinogenesis by the cinnamon-derived dietary factor cinnamaldehyde. Cancer Prev Res (Phila) 8(5):444-454.