Efficacy of geraniol but not of beta-ionone or their combination for the chemoprevention of rat colon carcinogenesis
ABSTRACT beta-ionone (beta I), 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 beta I 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 beta I (16 mg/100 g body weight), GO (25 mg/100 g body weight), beta I 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 beta I (91 +/- 11 and 14 +/- 3) and beta I+GO groups (96 +/- 5 and 19 +/- 2). Apoptosis level, identified by classical apoptosis morphological criteria, was significantly higher in the GO group (1.64 +/- 0.06 apoptotic cells/mm(2)) compared to control (0.91 +/- 0.07 apoptotic cells/mm(2)) in the distal colon. The GO group presented a 0.7-fold reduction in Bcl-2 protein expression (Western blot) compared to control. Colonic mucosa concentrations of beta I and GO (gas chromatography/mass spectrometry) were higher in the beta I and GO groups, respectively, compared to the control and beta I+GO groups. Therefore, GO, but not beta I, represents a potential chemopreventive agent in colon carcinogenesis. Surprisingly, the combination of isoprenoids does not represent an efficient chemopreventive strategy.