Quercetin enhances tumorigenicity induced by N-ethyl-N′-nitro-N-nitrosoguanidine in the duodenum of mice

Abstract

Quercetin, a flavonoid, widely distributed in many fruits and vegetables, is well known to have an antitumor effect despite its mutagenicity. In this study, we examined the effect of dietary quercetin on duodenum-tumorigenicity of mice induced by a chemical carcinogen, N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG). Eight-week-old male C57BL/6 mice were divided into 4 groups; ENNG without quercetin (group A), ENNG with 0.2% quercetin (group B), ENNG with 2% quercetin (group C), and 2% quercetin without ENNG (group D). ENNG was given in drinking water for the first 4 weeks, and thereafter quercetin was given in a mixed diet. At week 20, the average number of duodenal tumors per mouse was significantly higher in group C (mean±SE, 7.26±1.75, p<0.05) than in group A (2.32±0.31). The size of the duodenal tumors increased significantly in group B (1.79±0.09 mm, p<0.001) compared with group A (1.43±0.09 mm). In contrast, no duodenal tumor was induced in group D. The present findings suggest that excessive intake of quercetin occasionally is a risk factor for carcinogenesis of some specific organs such as the upper intestine.

Safety Aspects of the Use of Quercetin as a Dietary Supplement

“…Most studies revealed no or even chemo‐preventive effects of quercetin (details see). However, a few studies using different carcinogens (N‐ethyl‐N’‐nitro‐N‐nitrosoguanidin, azoxymethane, nitrosomethylurea or 17β‐estradiol) reported also an enhanced tumor development in duodenum, colon, pancreas, kidney or mammary glands of rodents after quercetin treatment with 0.2 to 3.4 % in feed (corresponding to approximately 150 to 3400 mg per kg bw and day). Two of these studies started the quercetin treatment in pregnant rats continuing in their offspring and investigated the tumorigenesis in the offspring .…”

Phytocompounds targeting epigenetic modulations: an assessment in cancer

“…The pro-oxidant nature of curcumin would increase cellular ROS levels at higher doses, potentially contributing to carcinogenesis ( López-Lázaro, 2008 ). Furthermore, excessive quercetin intake exacerbates tumorigenicity induced by a chemical carcinogen N-ethyl-N′-nitro-N-nitrosoguanidine (ENNG), in the duodenum of mice ( Matsukawa et al, 2002 ). While the immense health-promoting benefits of epigallocatechin-3-gallate, a study demonstrated that high dose administration of EGCG in mice resulted in hepatotoxicity correlated with inhibition of antioxidant enzymes and Nrf2 targeted genes ( Wang et al, 2015 ).…”