An assessment of the ability of quercetin to inhibit colon carcinogenesis

Abstract

Quercetin, one of the most widely consumed flavonoids in fruits and vegetables, purportedly reduces cancer incidence. Colon cancer is the second leading cause of death due to cancer in the United States. To establish whether quercetin would protect against colon cancer, using a 2X2 factorial design, 40 male Sprague-Dawley rats were fed diets containing 0 or 0.45% quercetin and injected with saline or azoxymethane (AOM, a colon specific carcinogen). Rats received the diets 3 wk prior to and 3 wk after the second injection of saline or AOM. The rats were terminated, the colon removed, cut in half longitudinally, and stained with 0.5% methylene blue to count aberrant crypt foci. Sections of the proximal and distal colon were fixed for immunohistochemical analysis of proliferation (PCNA) and apoptosis (TUNEL). Mucosal protein lysates were collected for western immunoblotting analysis of phosphatidylinositol 3-kinase (PI3K) p85 subunit, PI3K p85α subunit, and total Akt. Quercetin decreased (P=0.0246) the number of ACF with high multiplicity (ACF > 4). Quercetin reduced the total number of cells per crypt column (P=0.0440), the proliferative index using darkly stained cells (P=0.0346), and the extent of the proliferative zone (P=0.012). The apoptotic index was increased in response to dietary quercetin (P=0.0142) in the distal colon of AOM-injected rats. No significance was found in the proliferative index of lightly stained cells, or the steady state level of the proteins, PI3K p85 or PI3K p85α or total Akt. Therefore, quercetin may play a role in the chemopreventive effects of fruits and vegetables against colon carcinogenesis, through changes in cell proliferation and apoptosis. However, those changes do not occur because of an effect on the steady state level of PI3K or Akt expression.