Quercetin inhibits p21-ras expression in human colon cancer cell lines andin primary colorectal tumors

Immunocytochemical studies have revealed that 10 mu M quercetin reduced the steady state levels of p21-ras proteins in both colon cancer cell lines an d primary colorectal tumors. These findings were confirmed by Western blot and flow cytometric analysis showing that the inhibition of p21-ras express ion by quercetin was time- and concentration-dependent. Twenty-four-hour tr eatment with 10 mu M quercetin reduced p21-ras levels to about 50% of contr ol values. Quercetin was similarly effective in inhibiting the expression o f K-, H-, and N-ras proteins. Moreover, the effect of quercetin on ros onco gene expression was not dependent on the cell cycle position of colon cance r cells and appeared to be specific and not merely a consequence of overall inhibition of protein synthesis. Northern blot analysis revealed that quer cetin produced in colon cancer cells an early (30 min) reduction of the ste ady state levels of K-, H-, and N-ras mRNAs. This reduction was also presen t after 6 hr of flavonoid treatment. These effects of quercetin suggest a p ossible chemopreventive role for this compound in colorectal carcinogenesis . (C) 2000 Wiley-Liss, Inc.