Carrot intake and risk of colorectal cancer:A prospective cohort study of 57,053 Danes

Carrots are consumed worldwide. Several meta-analysis studies on carrot consumption have indicated that carrots play a central role as a protecting vegetable against development of different types of cancers. A cancer-preventive role of carrots is plausible because they are the main dietary source of the bioactive polyacetylenic oxylipins falcarinol (FaOH) and falcarindiol (FaDOH), which have shown anti-proliferative and anti-inflammatory activity in numerous in vitro studies. In addition, purified FaOH and FaDOH have, in recent studies in colorectal cancer (CRC)-primed rats, demonstrated an anti-neoplastic effect in a dose-dependent manner. The mechanisms of action for this effect appears to be due to inhibition of pro-inflammatory and transcription factor biomarkers for inflammation and cancer. However, studies of the CRC-preventive effect of carrots in a large cohort are still missing. We therefore examined the risk of being diagnosed with CRC as predicted by intake of carrots in a Danish population of 57,053 individuals with a long follow-up. Self-reported intake of raw carrots at a baseline of 2–4 carrots or more each week (>32 g/day) was associated with a 17% decrease in risk of CRC with a mean follow-up of >18 years, compared to individuals with no intake of raw carrots even after extensive model adjustments (HR 0.83 CI 95% 0.71; 0.98). An intake below 2–4 carrots each week (<32 g/day) was not significantly associated with reduced risk of CRC (HR 0.93 CI 95% 0.82; 1.06). The results of this prospective cohort study clearly support the results from studies in cancer-primed rats for CRC and hence a CRC-preventive effect of carrots

Effect of the dietary polyacetylenes falcarinol and falcarindiol on the gut microbiota composition in a rat model of colorectal cancer

Abstract Objectives (3R)-Falcarinol (FaOH) and (3R,8S)-falcarindiol (FaDOH) have previously been shown to reduce the number of neoplastic lesions and the growth rate of polyps in the colon of azoxymethane (AOM) treated rats. Based on previous investigations, it appears that different mechanisms of actions are involved in the antineoplastic effect of FaOH and FaDOH. One mechanism of action may be related to the antibacterial effect of FaOH and FaDOH and thus their effect on the gut microbiota. This study aimed to determine the effect of FaOH and FaDOH on gut microbiota composition of AOM treated rats. Results Azoxymethane treated rats were fed either a standard rat diet or a rat diet supplemented with FaOH and FaDOH. The gut microbiota of AOM-induced rats was determined by 16S rRNA gene-amplicon sequencing. Analysis of fecal cecum samples demonstrated a significant gut microbiota change in rats receiving standard rat diet supplemented with FaOH and FaDOH compared with the control group that only received the rat diet. Comparison of the gut microbiota of rats who developed large neoplasms in the colon with rats without large neoplasms showed that the gut microbiota was significantly different in rats who developed large colon neoplasms compared to rats with no macroscopic colon neoplasms

Dietary polyacetylenic oxylipins falcarinol and falcarindiol prevent inflammation and colorectal neoplastic transformation:A mechanistic and dose-response study in a rat model

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−1 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) and large 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