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Research Articles: Therapeutics, Targets, and Development

β-Ionone inhibits colonic aberrant crypt foci formation in rats, suppresses cell growth, and induces retinoid X receptor- in human colon cancer cells

¹ Department of Medicine, Hem-Onc Section, OU Cancer Institute, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma and ² Chemopreventive Agent Development Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland

Requests for reprints: Chinthalapally V. Rao, Department of Medicine, Hem-Onc Section, OU Cancer Institute, University of Oklahoma Health Sciences Center, 975 Northeast 10th Street, BRC Building, Room 1203, Oklahoma City, OK 73104. Phone: 405-271-3224. E-mail: cv-rao{at}ouhsc.edu

Abstract

β-Ionone, an end-ring analogue of β-carotenoid, which is a constituent of vegetables and fruits, has been analyzed for colon cancer chemoprevention and treatment. β-Ionone induced cell growth inhibition and apoptosis in human colon cancer HCT116 cell line. We tested the in vivo chemopreventive efficacy in rat colon carcinogenesis model using aberrant crypt foci (ACF) as endpoint marker. HCT116 cells treated with subtoxic concentrations of β-ionone resulted dose-dependent cell growth suppression with G₁-S-phase growth arrest and significant induction of apoptosis. β-Ionone up-regulated expression of retinoid X receptor- mRNA dose-dependently in HCT116 cells. To evaluate inhibitory properties of β-ionone on colonic ACF, 7-week-old male F344 rats were fed experimental diets containing 0%, 0.1%, or 0.2% β-ionone. After 1 week, rats received s.c. injections of azoxymethane, 15 mg/kg body weight, once weekly for 2 weeks. Rats were continued on respective experimental diets and sacrificed 8 weeks after the azoxymethane treatment. Colons were evaluated histopathologically for ACF. Administration of dietary 0.1% and 0.2% β-ionone significantly suppressed total colonic ACF formation up to 34% to 38% (P < 0.0002 to P < 0.0009), respectively, when compared with control group. Importantly, rats fed β-ionone showed >55% inhibition (P < 0.0001) of foci containing four or more aberrant crypts. Results from in vitro and in vivo bioassay clearly suggest that β-ionone could be further developed for prevention and treatment of colon cancer. [Mol Cancer Ther 2008;7(1):181–90]

Grant support: National Cancer Institute grants N01CN-53300, CN-6500, and R01CA-94962.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 8/ 3/07; revised 10/31/07; accepted 11/29/07.