The cinnamon-derived dietary factor cinnamic aldehyde activates the Nrf2-dependent antioxidant response in human epithelial colon cells.
Colorectal cancer (CRC) is a major cause of tumor-related morbidity and mortality worldwide. Recent research suggests that pharmacological intervention using dietary factors that activate the redox sensitive Nrf2/Keap1-ARE signaling pathway may represent a promising strategy for chemoprevention of human cancer including CRC. In our search for dietary Nrf2 activators with potential chemopreventive activity targeting CRC, we have focused our studies on trans-cinnamic aldehyde (cinnamaldeyde, CA), the key flavor compound in cinnamon essential oil. Here we demonstrate that CA and an ethanolic extract (CE) prepared from Cinnamomum cassia bark, standardized for CA content by GC-MS analysis, display equipotent activity as inducers of Nrf2 transcriptional activity. In human colon cancer cells (HCT116, HT29) and non-immortalized primary fetal colon cells (FHC), CA- and CE-treatment upregulated cellular protein levels of Nrf2 and established Nrf2 targets involved in the antioxidant response including heme oxygenase 1 (HO-1) and gamma-glutamyl-cysteine synthetase (gamma-GCS, catalytic subunit). CA- and CE-pretreatment strongly upregulated cellular glutathione levels and protected HCT116 cells against hydrogen peroxide-induced genotoxicity and arsenic-induced oxidative insult. Taken together our data demonstrate that the cinnamon-derived food factor CA is a potent activator of the Nrf2-orchestrated antioxidant response in cultured human epithelial colon cells. CA may therefore represent an underappreciated chemopreventive dietary factor targeting colorectal carcinogenesis.
Wondrak
Georg Thomas
GT
Department of Pharmacology and Toxicology, College of Pharmacy, Arizona Cancer Center, University of Arizona, Tucson, AZ 85724, USA. wondrak@pharmacy.arizona.edu
Villeneuve
Nicole F
NF
Lamore
Sarah D
SD
Bause
Alexandra S
AS
Jiang
Tao
T
Zhang
Donna D
DD
D000171:Acrolein / Q000031:analogs & derivatives* / Q000494:pharmacology; D000975:Antioxidants; D045744:Cell Line, Tumor; D018890:Chemoprevention / Q000379:methods; D002935:Cinnamomum zeylanicum; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D019587:Dietary Supplements; D004847:Epithelial Cells; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D010084:Oxidation-Reduction; D015398:Signal Transduction
D000975:Antioxidants; D051267:NF-E2-Related Factor 2; D000171:Acrolein; C012843:cinnamaldehyde