beta-ionone and Colonic-Neoplasms

β-ionone (βI), a cyclic isoprenoid, and geraniol (GO), an acyclic monoterpene, represent a promising class of dietary chemopreventive agents against cancer, whose combination could result in synergistic anticarcinogenic effects. The chemopreventive activities of βI and GO were evaluated individually or in combination during colon carcinogenesis induced by dimethylhydrazine in 48 3-week-old male Wistar rats (12 per group) weighing 40-50 g. Animals were treated for 9 consecutive weeks with βI (16 mg/100 g body weight), GO (25 mg/100 g body weight), βI combined with GO or corn oil (control). Number of total aberrant crypt foci (ACF) and of ACF ≥4 crypts in the distal colon was significantly lower in the GO group (66 ± 13 and 9 ± 2, respectively) compared to control (102 ± 9 and 17 ± 3) and without differences in the βI (91 ± 11 and 14 ± 3) and βI+GO groups (96 ± 5 and 19 ± 2). Apoptosis level, identified by classical apoptosis morphological criteria, in the distal colon was significantly higher in the GO group (1.64 ± 0.06 apoptotic cells/mm²) compared to control (0.91 ± 0.07 apoptotic cells/mm²). The GO group presented a 0.7-fold reduction in Bcl-2 protein expression (Western blot) compared to control. Colonic mucosa concentrations of βI and GO (gas chromatography/mass spectrometry) were higher in the βI and GO groups, respectively, compared to the control and βI+GO groups. Therefore, GO, but not βI, represents a potential chemopreventive agent in colon carcinogenesis. Surprisingly, the combination of isoprenoids does not represent an efficient chemopreventive strategy.

Topics: Acyclic Monoterpenes; Animals; Anticarcinogenic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinogens; Colon; Colonic Neoplasms; Dimethylhydrazines; Drug Screening Assays, Antitumor; Intestinal Mucosa; Male; Norisoprenoids; Rats; Rats, Wistar; Terpenes

Beta-ionone, an end-ring analogue of beta-carotenoid, which is a constituent of vegetables and fruits, has been analyzed for colon cancer chemoprevention and treatment. beta-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 beta-ionone resulted dose-dependent cell growth suppression with G1-S-phase growth arrest and significant induction of apoptosis. beta-Ionone up-regulated expression of retinoid X receptor-alpha mRNA dose-dependently in HCT116 cells. To evaluate inhibitory properties of beta-ionone on colonic ACF, 7-week-old male F344 rats were fed experimental diets containing 0%, 0.1%, or 0.2% beta-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% beta-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 beta-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 beta-ionone could be further developed for prevention and treatment of colon cancer.

Topics: Animals; Azoxymethane; Cell Line, Tumor; Cell Proliferation; Colonic Neoplasms; Gene Expression Regulation, Neoplastic; Humans; Male; Molecular Structure; Norisoprenoids; Rats; Rats, Inbred F344; Retinoid X Receptor alpha; RNA, Messenger