Quercetin, but Not Its Glycosidated Conjugate Rutin, Inhibits Azoxymethane-Induced Colorectal Carcinogenesis in F344 Rats

A.A. Dihal, V.C.J. de Boer, H. van der Woude, C. Tilburgs, J.P. Bruintjes, G.M. Alink, I.M.C.M. Rietjens, R.A. Woutersen, R.H. Stierum

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Abstract

The effect of the flavonoid quercetin and its conjugate rutin was investigated on (biomarkers of) colorectal cancer (CRC). Male F344 rats (n = 42/group) were fed 0, 0.1, 1, or 10 g quercetin/kg diet or 40 g rutin/kg diet. Two wk after initial administration of experimental diets, rats were given 2 weekly subcutaneous injections with 15 mg/kg body wt azoxymethane (AOM). At wk 38 post-AOM, quercetin dose dependently (P <0.05) decreased the tumor incidence, multiplicity, and size, whereas tumor incidences were comparable in control (50%) and rutin (45%) groups. The number of aberrant crypt foci (ACF) in unsectioned colons at wk 8 did not correlate with the tumor incidence at wk 38. Moreover, at wk 8 post-AOM, the number and multiplicity of ACF with or without accumulation of ß-catenin were not affected by the 10 g quercetin/kg diet. In contrast, another class of CRC-biomarkers, ß-catenin accumulated crypts, contained less ß-catenin than in controls (P <0.05). After enzymatic deconjugation, the plasma concentration of 3¿-O-methyl-quercetin and quercetin at wk 8 was inversely correlated with the tumor incidence at wk 38 (r = -0.95, P ¿ 0.05). Rats supplemented with 40 g rutin/kg diet had only 30%of the (3¿-O-methyl-) quercetin concentration of 10 g quercetin/kg diet-fed rats (P <0.001). In conclusion, quercetin, but not rutin, at a high dose reduced colorectal carcinogenesis in AOM-treated rats, which was not reflected by changes in ACF-parameters. The lack of protection by rutin is probably due to its low bioavailability
Original languageEnglish
Pages (from-to)2862-2867
JournalThe Journal of Nutrition
Volume136
Issue number11
DOIs
Publication statusPublished - Nov 2006

Keywords

  • aberrant crypt foci
  • colon carcinogenesis
  • cell-proliferation
  • treated rats
  • cancer
  • bioavailability
  • flavonoids
  • carcinomas
  • expression
  • epithelium

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