Response of Apcmin and A33ΔNβ-cat mutant mice to treatment with tea, sulindac, and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)

Gayle A. Orner, Wan Mohaiza Dashwood, Carmen A. Blum, G. Darío Díaz, Qingjie Li, Mohamad Al-Fageeh, Niall Tebbutt, Joan K. Heath, Matthias Ernst, Roderick H. Dashwood

Research output: Contribution to journalArticle

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Abstract

There is growing interest in the potential health benefits of tea, and a recent report described the potent antimutagenic activity of white tea in comparison with green tea against several heterocyclic amines, including 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) [Mutat. Res. 495 (2001) 61]. We compared the inhibitory effects of white and green teas with sulindac, a nonsteroidal anti-inflammatory agent, in two different mouse models of intestinal tumorigenesis. In the Apcmin mouse, white and green teas given at human-relevant concentrations (1.5% w/v, 2-min brew), and sulindac (80ppm in the drinking water), each suppressed polyp formation by ∼50%, and the combination of white tea plus sulindac was more effective than either treatment alone (P=0.05). Mice expressing an N-terminally truncated, oncogenic version of β-catenin (A33ΔNβ-cat mutant mice) developed colonic aberrant crypt foci (ACF) spontaneously, but PhIP treatment increased the incidence and number of ACF per colon. In the normal-looking intestinal mucosa of Apcmin and A33ΔNβ-cat mice, white tea plus sulindac treatment markedly attenuated the expression of β-catenin protein, and this was recapitulated in vitro in cells transiently transfected with β-catenin plus Tcf-4 and treated with tea or the major tea polyphenol epigallocatechin-3-gallate (EGCG). Expression of a β-catenin/Tcf reporter was inhibited by EGCG in the transfected cells, and the β-catenin/Tcf target genes cyclin D1 and c-jun were downregulated in vivo by tea plus sulindac treatment. Collectively, the data support a chemopreventive role for tea and sulindac against intermediate and late stages of colon cancer, via effects on the β-catenin/Tcf signaling pathway.

Original languageEnglish (US)
Pages (from-to)121-127
Number of pages7
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume506-507
DOIs
StatePublished - Sep 30 2002
Externally publishedYes

Fingerprint

Sulindac
Tea
Cats
Catenins
Aberrant Crypt Foci
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine
bcl-1 Genes
Polyphenols
Non-Steroidal Anti-Inflammatory Agents
Insurance Benefits
Intestinal Mucosa
Polyps
Drinking Water
Colonic Neoplasms
Amines
Colon
Carcinogenesis
Down-Regulation

Keywords

  • β-Catenin
  • Aberrant crypt foci
  • APC
  • Heterocyclic amines
  • Polyps
  • Tcf/Lef

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Molecular Biology

Cite this

Response of Apcmin and A33ΔNβ-cat mutant mice to treatment with tea, sulindac, and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). / Orner, Gayle A.; Dashwood, Wan Mohaiza; Blum, Carmen A.; Díaz, G. Darío; Li, Qingjie; Al-Fageeh, Mohamad; Tebbutt, Niall; Heath, Joan K.; Ernst, Matthias; Dashwood, Roderick H.

In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 506-507, 30.09.2002, p. 121-127.

Research output: Contribution to journalArticle

Orner, Gayle A. ; Dashwood, Wan Mohaiza ; Blum, Carmen A. ; Díaz, G. Darío ; Li, Qingjie ; Al-Fageeh, Mohamad ; Tebbutt, Niall ; Heath, Joan K. ; Ernst, Matthias ; Dashwood, Roderick H. / Response of Apcmin and A33ΔNβ-cat mutant mice to treatment with tea, sulindac, and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis. 2002 ; Vol. 506-507. pp. 121-127.
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AU - Orner, Gayle A.

AU - Dashwood, Wan Mohaiza

AU - Blum, Carmen A.

AU - Díaz, G. Darío

AU - Li, Qingjie

AU - Al-Fageeh, Mohamad

AU - Tebbutt, Niall

AU - Heath, Joan K.

AU - Ernst, Matthias

AU - Dashwood, Roderick H.

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