Quercetin, but not its glycosidated conjugate rutin, inhibits azoxymethane-induced colorectal carcinogenesis in F344 rats.
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 beta-catenin were not affected by the 10 g quercetin/kg diet. In contrast, another class of CRC-biomarkers, beta-catenin accumulated crypts, contained less beta-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.
Dihal
Ashwin A
AA
TNO Quality of Life, Business Unit Biosciences, Zeist, The Netherlands. ashwin.dihal@tno.nl
de Boer
Vincent C J
VC
van der Woude
Hester
H
Tilburgs
Chantal
C
Bruijntjes
Joost P
JP
Alink
Gerrit M
GM
Rietjens
Ivonne M C M
IM
Woutersen
Ruud A
RA
Stierum
Rob H
RH
D000818:Animals; D001397:Azoxymethane / Q000633:toxicity; D001835:Body Weight; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D019587:Dietary Supplements; D008297:Male; D011230:Precancerous Conditions / Q000517:prevention & control; D011794:Quercetin / Q000097:blood / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344; D012431:Rutin / Q000627:therapeutic use*; D051176:beta Catenin / Q000378:metabolism
D051176:beta Catenin; D012431:Rutin; D011794:Quercetin; D001397:Azoxymethane