Abstract
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.
Highlights
Colon cancer, which is the second most prevalent type of cancer in the world, is an important public health problem that is related to life style, especially eating habits [1].Bioactive compounds present in foods, such as isoprenic derivatives found in fruits and vegetables, are potential chemopreventive agents against cancer [2,3]
GO inhibited the growth of mammary and pancreatic neoplasms in rats and hamsters, respectively [11,12], and proved to be an effective adjuvant in the treatment with 5-fluorouracil of human colorectal cancer cells transplanted in Swiss nu/ nu mice [13]. βI reduced the incidence of mammary neoplasms in rats [3,11] and, more recently, it was shown to inhibit the number and size of preneoplastic lesions (PNLs) in the colon when administered in the diet to F344
There was no difference in the number of aberrant crypt foci (ACF)
Summary
Colon cancer, which is the second most prevalent type of cancer in the world, is an important public health problem that is related to life style, especially eating habits [1].Bioactive compounds present in foods, such as isoprenic derivatives found in fruits and vegetables, are potential chemopreventive agents against cancer [2,3]. Promising dietary isoprenoids are β-ionone (βI), a cyclic isoprenoid, the product of β-carotene degradation, which is present mainly in grapes and wine aromatizers, and geraniol (GO), an acyclic monoterpene, which is an important constituent of the essential oils of ginger, lemon, lime, orange, and nutmeg (Figure 1). Both compounds are of interest to the detergent, perfume and food industries because of their floral aromatics and antifungal and antioxidant properties [4,5]. GO inhibited the growth of mammary and pancreatic neoplasms in rats and hamsters, respectively [11,12], and proved to be an effective adjuvant in the treatment with 5-fluorouracil of human colorectal cancer cells transplanted in Swiss nu/ nu mice [13]. βI reduced the incidence of mammary neoplasms in rats [3,11] and, more recently, it was shown to inhibit the number and size of preneoplastic lesions (PNLs) in the colon when administered in the diet to F344
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