Targeting colorectal carcinogenesis using a cinnamon-derived food factor

DESCRIPTION (provided by applicant): Colorectal cancer (CRC) is a major cause of tumor-related morbidity and mortality worldwide. Recent research strongly suggests that the redox-sensitive transcription factor Nrf2 (nuclear factor-E2-related factor 2) is a promising molecular target for chemoprevention of inflammation-driven colorectal carcinogenesis. The ground bark of Cinnamomum aromaticum (cassia) and Cinnamomum verum (Ceylon cinnamon), commonly referred to as 'cinnamon', is one of the three most consumed spices in the world, yet health effects of cinnamon consumption have remained mostly unexplored at the molecular level. Recently, we have identified the cinnamon-derived food factor cinnamaldehyde as the key principle in cinnamon powder responsible for potent induction of the Nrf2-regulated antioxidant response in human colon cells, conferring cytoprotection against subsequent oxidative and genotoxic insult. We propose exploratory research that tests the overall hypothesis that cinnamaldehyde represents a potent chemopreventive dietary factor targeting colorectal carcinogenesis through modulation of Nrf2-orchestrated cytoprotective mechanisms. To test this hypothesis, the following specific aims will be pursued: Aim #1. To define the specific molecular targets involved in Nrf2-activation by cinnamaldehyde in colorectal epithelial cells. Aim #2. To test feasibility of cinnamaldehyde-based intervention targeting colorectal carcinogenesis in an accepted murine model and to determine mechanistic involvement of Nrf2 in cinnamaldehyde chemopreventive activity. Successful completion of this project will generate critical proof-of-principle data guiding the rational design of future preclinical and clinical studies that aim at developing cinnamaldehyde for chemopreventive intervention targeting human colorectal carcinogenesis.