title: Dietary polyacetylenes, falcarinol and falcarindiol, isolated from carrots prevents the formation of neoplastic lesions in the colon of azoxymethane-induced rats.
abstract: Falcarinol (FaOH) and falcarindiol (FaDOH) are found in many food plants of the Apiaceae family. Carrots are a major dietary source of these polyacetylenes. Feeding azoxymethane (AOM)-induced rats with carrots and purified FaOH have previously been shown to inhibit neoplastic transformations in the colon. FaOH and FaDOH have also shown to have a synergistic effect in vitro, resulting in a significant increased cytotoxic activity. Based on these findings the antineoplastic effect of FaOH and FaDOH (purity > 99%) was investigated in the AOM-induced rat model. Twenty rats received rat diet containing 7 μg FaOH per g feed and 7 μg FaDOH per g feed and 20 rats were controls receiving only rat diet. Then carcinogenesis was induced in all 40 rats with the carcinogen AOM. All animals received the designated diet for 2 weeks before AOM induction and continued on the designated diet throughout the experiment. Rats were euthanized 18 weeks after the first AOM injection and macroscopic polyp/cancers were measured, harvested and stained for histology. The difference in sizes of aberrant crypt foci (ACF) were analysed in a Wilcoxon rank sum test, in which the median number of small ACF was 218 in controls and 145 in polyacetylene treated rats (P < 0.001). Fifteen control rats and 8 treated rats had macroscopic tumors (P = 0.027). The number of tumors larger than 3 mm were 6 and 1 in control and treated rats, respectively (P = 0.032). In conclusion dietary supplements with FaOH and FaDOH reduced the number of neoplastic lesions as well as the growth rate of the polyps suggesting a preventive effect of FaOH and FaDOH on the development of colorectal cancer.
authors.affiliation: Department of Clinical Research, University of Southern Denmark, Winsløwparken 19, DK-5000 Odense C, Denmark and Department of Surgery A, Odense University Hospital, Valdemarsgade 53, DK-5700 Svendborg, Denmark. Morten.Kobaek.Larsen@rsyd.dk.
authors.forename: Morten
authors.identifier: http://orcid.org/0000-0002-5097-9283
authors.initials: M
authors.lastname: Kobaek-Larsen
authors.affiliation: Department of Chemical Engineering, Biotechnology and Environmental Technology, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
authors.forename: Rime B
authors.initials: RB
authors.lastname: El-Houri
authors.affiliation: Department of Chemical Engineering, Biotechnology and Environmental Technology, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
authors.forename: Lars P
authors.initials: LP
authors.lastname: Christensen
authors.affiliation: Department of Clinical Research, University of Southern Denmark, Winsløwparken 19, DK-5000 Odense C, Denmark and Department of Surgery A, Odense University Hospital, Valdemarsgade 53, DK-5700 Svendborg, Denmark. Morten.Kobaek.Larsen@rsyd.dk.
authors.forename: Issam
authors.initials: I
authors.lastname: Al-Najami
authors.affiliation: Department of Chemical Engineering, Biotechnology and Environmental Technology, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
authors.forename: Xavier
authors.identifier: http://orcid.org/0000-0002-4841-7011
authors.initials: X
authors.lastname: Fretté
authors.affiliation: Department of Clinical Research, University of Southern Denmark, Winsløwparken 19, DK-5000 Odense C, Denmark and Department of Surgery A, Odense University Hospital, Valdemarsgade 53, DK-5700 Svendborg, Denmark. Morten.Kobaek.Larsen@rsyd.dk.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Baatrup
mesh_terms: D000821:Animal Feed / Q000032:analysis; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage* / Q000378:metabolism; D001397:Azoxymethane / Q000633:toxicity*; D003106:Colon / Q000187:drug effects / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D018552:Daucus carota / Q000737:chemistry* / Q000378:metabolism; D053280:Diynes / Q000008:administration & dosage* / Q000378:metabolism; D005233:Fatty Alcohols / Q000008:administration & dosage* / Q000378:metabolism; D006801:Humans; D008297:Male; D010936:Plant Extracts / Q000008:administration & dosage*; D053279:Polyynes / Q000008:administration & dosage* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D016588:Anticarcinogenic Agents; D053280:Diynes; D005233:Fatty Alcohols; D010936:Plant Extracts; C018541:falcarinol; D053279:Polyynes; C034379:falcarindiol; D001397:Azoxymethane