TY - JOUR T1 - The Ellagic Acid Derivative 4,4′-Di-<em>O</em>-Methylellagic Acid Efficiently Inhibits Colon Cancer Cell Growth through a Mechanism Involving WNT16 JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 433 LP - 444 DO - 10.1124/jpet.114.221796 VL - 353 IS - 2 AU - Ana Ramírez de Molina AU - Teodoro Vargas AU - Susana Molina AU - Jenifer Sánchez AU - Jorge Martínez-Romero AU - Margarita González-Vallinas AU - Roberto Martín-Hernández AU - Ruth Sánchez-Martínez AU - Marta Gómez de Cedrón AU - Alberto Dávalos AU - Luca Calani AU - Daniele Del Rio AU - Antonio González-Sarrías AU - Juan Carlos Espín AU - Francisco A. Tomás-Barberán AU - Guillermo Reglero Y1 - 2015/05/01 UR - http://jpet.aspetjournals.org/content/353/2/433.abstract N2 - 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. This study aimed 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. 4,4′-DiOMEA was 13-fold more effective than other compounds of the same family. In addition, 4,4′-DiOMEA was very active against colon cancer cells resistant to the chemotherapeutic agent 5-fluoracil, whereas no effect was observed in nonmalignant colon cells. Moreover, no correlation between antiproliferative and antioxidant activities was found, further supporting that structure differences might result in dissimilar 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. ER -