RT info:eu-repo/semantics/article T1 The ellagic acid derivative 4,4′-Di-O-methylellagic acid efficiently inhibits colon cancer cell growth through a mechanism involving WNT16 A1 Ramírez de Molina, Ana A1 Vargas, Teodoro A1 Molina, Susana A1 Sánchez, Jenifer A1 Martínez Romero, Jorge A1 González-Vallinas Garrachón, Margarita A1 Martín Hernández, Roberto A1 Sánchez Martínez, Ruth A1 Gómez de Cedrón, Marta A1 Dávalos, Alberto A1 Calani, Luna A1 Rio, Daniele del A1 González Sarrías, Antonio A1 Espín, Juan Carlos A1 Tomás Barberán, Francisco A. A1 Reglero, Guillermo K1 Cáncer K1 Ácido elágico K1 3207.13 Oncología AB 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. PB American Society for Pharmacology and Experimental Therapeutics (ASPET) SN 0022-3565 YR 2015 FD 2015 LK http://uvadoc.uva.es/handle/10324/42587 UL http://uvadoc.uva.es/handle/10324/42587 LA eng NO Journal of Pharmacology and Experimental Therapeutics, 2015, vol. 353, n. 2, p. 433-444 NO Producción Científica DS UVaDOC RD 25-abr-2024