Inhibitory Effects of Feeding with Carrots or (−)-Falcarinol on Development of Azoxymethane-Induced Preneoplastic Lesions in the Rat Colon

Biomedical Laboratory, University of Southern Denmark, Winsloewparken 23, DK-5000 Odense C, Denmark.
Journal of Agricultural and Food Chemistry (Impact Factor: 2.91). 04/2005; 53(5):1823-7. DOI: 10.1021/jf048519s
Source: PubMed


The effects of intake of dietary amounts of carrot or corresponding amounts of (-)-(3R)-falcarinol from carrots on development of azoxymethane (AOM)-induced colon preneoplastic lesions were examined in male BDIX rats. Three groups of eight AOM-treated rats were fed the standard rat feed Altromin supplemented with either 10% (w/w) freeze-dried carrots with a natural content of 35 mug falcarinol/g, 10% maize starch to which was added 35 mug falcarinol/g purified from carrots, or 10% maize starch (control). After 18 weeks, the animals were euthanized and the colon was examined for tumors and aberrant crypt foci (ACF), which were classified into four size classes. Although the number of small ACF was unaffected by the feeding treatments, the numbers of lesions as a function of increasing size class decreased significantly in the rats that received one of the two experimental treatments, as compared with the control treatment. This indicates that the dietary treatments with carrot and falcarinol delayed or retarded the development of large ACF and tumors. The present study provides a new perspective on the known epidemiological associations between high intake of carrots and reduced incidence of cancers.

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    • "). The inhibition of cancer cell of ginseng partially (Kim et al., 2002; Matsunaga et al., 1990; Wang and Yuan, 2008) and of carrot wholly (Kobaek-Larsen et al., 2005; Susanne et al., 2003) resulted from the cytotoxic activities of the polyacetylenic compounds. The selective cytotoxic activity towards cancer cells indicates that these types of polyacetylenes and the herbs or vegetables that contain them may be valuable in the treatment and/or prevention of different types of cancer (Christensen and Brandt, 2006). "
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    ABSTRACT: Devil's Club (Oplopanax horridus) is one of the most important spiritual and medicinal plants to many indigenous peoples of Alaska and the Pacific Northwest. It is widely used for external and internal infections as well as arthritis, respiratory ailments, digestive tract ailments, broken bones, fever, headaches, and cancer. To investigate hydrophobic constituents and their potential anticancer activity from Devil's Club, Oplopanax horridus. The root bark extract of Oplopanax horridus was isolated by chromatographic techniques. Structures of isolated compounds were identified by spectroscopic methods and comparison with published data. The anti-proliferation of isolated hydrophobic constituents in human breast cancer MCF-7 cells, human colon cancer SW-480 and HCT-116 cells were tested. The potential mechanism of anti-proliferation was also investigated using cell cycle and apoptosis assays. Six compounds were isolated and structurally identified as 9,17-octadecadiene-12,14-diyne-1,11,16-triol, 1-acetate (1), oplopandiol acetate (2), falcarindiol (3), oplopandiol (4), trans-nerolidol (5) and t-cadinol (6). These compounds showed potential anticancer activities on human breast cancer and colon cancer cells, of which compound 3 possesses the strongest activity. Further cell cycle and apoptosis tests by flow cytometry showed the polyacetylenes 1-4 induced HCT-116 cell arresting in G2/M phase and inhibited proliferation by the induction of apoptosis at both earlier and later stages. These results provide promising baseline information for the potential use of Oplopanax horridus, as well as some of the isolated compounds in the treatment of cancer.
    Journal of ethnopharmacology 10/2010; 132(1):280-5. DOI:10.1016/j.jep.2010.08.026 · 3.00 Impact Factor
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    • "including skin irritation (dermatitis) and potential anti-carcinogenic effects in colon [10] [11] [12] [13]. However, to date no protein targets for falcarinol have been identified. "
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    ABSTRACT: The skin irritant polyyne falcarinol (panaxynol, carotatoxin) is found in carrots, parsley, celery, and in the medicinal plant Panax ginseng. In our ongoing search for new cannabinoid (CB) receptor ligands we have isolated falcarinol from the endemic Sardinian plant Seseli praecox. We show that falcarinol exhibits binding affinity to both human CB receptors but selectively alkylates the anandamide binding site in the CB(1) receptor (K(i)=594nM), acting as covalent inverse agonist in CB(1) receptor-transfected CHO cells. Given the inherent instability of purified falcarinol we repeatedly isolated this compound for biological characterization and one new polyyne was characterized. In human HaCaT keratinocytes falcarinol increased the expression of the pro-allergic chemokines IL-8 and CCL2/MCP-1 in a CB(1) receptor-dependent manner. Moreover, falcarinol inhibited the effects of anandamide on TNF-alpha stimulated keratinocytes. In vivo, falcarinol strongly aggravated histamine-induced oedema reactions in skin prick tests. Both effects were also obtained with the CB(1) receptor inverse agonist rimonabant, thus indicating the potential role of the CB(1) receptor in skin immunopharmacology. Our data suggest anti-allergic effects of anandamide and that falcarinol-associated dermatitis is due to antagonism of the CB(1) receptor in keratinocytes, leading to increased chemokine expression and aggravation of histamine action.
    Biochemical pharmacology 03/2010; 79(12):1815-26. DOI:10.1016/j.bcp.2010.02.015 · 5.01 Impact Factor
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    • "In this study we have identified the fatty acid-derived natural product falcarinol which possesses a reactive polyyne structure, as new functional CB receptor ligand. Interestingly, falcarinol has previously been reported to exert pharmacological effects, including skin irritation (dermatitis) and potential anti-carcinogenic effects in colon [10] [11] [12] [13]. However, to date no protein targets for falcarinol have been identified. "

    Planta Medica 07/2009; 75(09). DOI:10.1055/s-0029-1234271 · 2.15 Impact Factor
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