The cinnamon-derived dietary factor cinnamic aldehyde activates the Nrf2-dependent antioxidant response in human epithelial colon cells

Georg T Wondrak, Nicole F. Villeneuve, Sarah D. Lamore, Alexandra S. Bause, Tao Jiang, Donna Zhang

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

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 γ-glutamyl-cysteine synthetase (γ-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.

Original languageEnglish (US)
Pages (from-to)3338-3355
Number of pages18
JournalMolecules
Volume15
Issue number5
DOIs
StatePublished - May 2010

Fingerprint

Cinnamomum zeylanicum
antioxidants
aldehydes
HCT116 Cells
Colorectal Neoplasms
Colon
Flavor compounds
Antioxidants
cancer
Epithelial Cells
Heme Oxygenase-1
Cinnamomum aromaticum
Arsenic
Volatile Oils
Ligases
cells
Hydrogen Peroxide
Glutathione
Cysteine
Tumors

Keywords

  • Antioxidant response
  • Cinnamic aldehyde
  • Colon cancer
  • Nrf2-activator

ASJC Scopus subject areas

  • Organic Chemistry
  • Medicine(all)

Cite this

The cinnamon-derived dietary factor cinnamic aldehyde activates the Nrf2-dependent antioxidant response in human epithelial colon cells. / Wondrak, Georg T; Villeneuve, Nicole F.; Lamore, Sarah D.; Bause, Alexandra S.; Jiang, Tao; Zhang, Donna.

In: Molecules, Vol. 15, No. 5, 05.2010, p. 3338-3355.

Research output: Contribution to journalArticle

Wondrak, Georg T ; Villeneuve, Nicole F. ; Lamore, Sarah D. ; Bause, Alexandra S. ; Jiang, Tao ; Zhang, Donna. / The cinnamon-derived dietary factor cinnamic aldehyde activates the Nrf2-dependent antioxidant response in human epithelial colon cells. In: Molecules. 2010 ; Vol. 15, No. 5. pp. 3338-3355.
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