Abstract

Ellagic acid (EA) and some derivatives have been reported to inhibit cancer cell proliferation, induce cell cycle arrest and modulate some important cellular processes related to cancer. The aim of this study was to identify possible structure-activity relationships of EA and some in vivo derivatives in their antiproliferative effect on both human colon cancer and normal cells, and to compare this activity with that of other polyphenols. Our results showed that 4,4'-Di-O-methylellagic acid (4,4'-DiOMEA) was the most effective compound in the inhibition of colon cancer cell proliferation, reaching 13-fold more effect than other compounds of the same family, being also very active against colon cancer cells resistant to the chemotherapeutic agent 5-Fluoracil whereas no effect was observed in non-malignant colon cells. Moreover, no correlation between antiproliferative and antioxidant activities was found further supporting that structure differences might result in dissimiliar molecular targets involved in their differential effects. Finally, microarray analysis revealed that 4,4'-DiOMEA modulated Wnt signaling, which might be involved in the potential antitumor action of this compound. Our results suggest that structural-activity differences between EA and 4,4'-DiOMEA might constitute the basis for a new strategy in anticancer drug discovery based on these chemical modifications.