Dietary Polyacetylenic Oxylipins Falcarinol and Falcarindiol Prevent Inflammation and Colorectal Neoplastic Transformation: A Mechanistic and Dose-Response Study in A Rat Model

• Published in: Nutrients 2019-09, Vol.11 (9), p.2223
• Main Authors: Kobaek-Larsen, Morten, Baatrup, Gunnar, KhataeiNotabi, Martine, El-Houri, Rime Bahij, Pipó-Ollé, Emma, Christensen Arnspang, Eva, Christensen, Lars Porskjær
• Format: Article
• Language: English
• Subjects: Aberrant Crypt Foci - metabolism; Aberrant Crypt Foci - pathology; Aberrant Crypt Foci - prevention & control; Activation; Alkylation; Animal tissues; Animals; Anti-inflammatory agents; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - pharmacology; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacology; Antioxidants; Apoptosis; Carcinogenesis; Carcinogens; Cell cycle; Colon - drug effects; Colon - metabolism; Colon - pathology; Colorectal cancer; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Colorectal Neoplasms - prevention & control; Cyclooxygenase-2; Cytokines; Cytokines - metabolism; Cytotoxicity; Diet; Disease; Disease prevention; Diynes - administration & dosage; Diynes - pharmacology; Enzymes; Fatty Alcohols - administration & dosage; Fatty Alcohols - pharmacology; Gene Expression Regulation, Neoplastic - drug effects; Inflammation; Inflammation - metabolism; Inflammation - prevention & control; Intestine; Male; Medical prognosis; Metabolism; Metabolites; Neoplasia; Neoplasms; Neoplasms, Experimental - metabolism; Neoplasms, Experimental - pathology; Neoplasms, Experimental - prevention & control; NF-κB protein; Nonsteroidal anti-inflammatory drugs; Rats; Rats, Inbred F344; Signal Transduction - drug effects; Tumor necrosis factor-TNF; Tumors
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu11092223

Falcarinol (FaOH) and falcarindiol (FaDOH) are cytotoxic and anti-inflammatory polyacetylenic oxylipins, which are commonly found in the carrot family (Apiaceae). FaOH and FaDOH have previously demonstrated a chemopreventive effect on precursor lesions of colorectal cancer (CRC) in azoxymethane (AOM)-induced rats. The purpose of the present study was to elucidate possible mechanisms of action for the preventive effect of FaOH and FaDOH on colorectal precancerous lesions and to determine how this effect was dependent on dose. Gene expression studies performed by RT-qPCR of selected cancer biomarkers in tissue from biopsies of neoplastic tissue revealed that FaOH and FaDOH downregulated NF-κβ and its downstream inflammatory markers TNFα, IL-6, and COX-2. The dose-dependent anti-neoplastic effect of FaOH and FaDOH in AOM-induced rats was investigated in groups of 20 rats receiving a standard rat diet (SRD) supplemented with 0.16, 0.48, 1.4, 7 or 35 µg FaOH and FaDOH g feed in the ratio 1:1 and 20 rats were controls receiving only SRD. Analysis of aberrant crypt foci (ACF) showed that the average number of small ACF (7 crypts) decreased with increasing dose of FaOH and FaDOH and that this inhibitory effect on early neoplastic formation of ACF was dose-dependent, which was also the case for the total number of macroscopic neoplasms. The CRC protective effects of apiaceous vegetables are mainly due to the inhibitory effect of FaOH and FaDOH on NF-κB and its downstream inflammatory markers, especially COX-2.