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The ellagic acid derivative 4,4'-di-O-methylellagic acid efficiently inhibits colon cancer cell growth through a mechanism involving WNT16

AuthorsRamírez de Molina, Ana; Vargas, Teodoro; Molina, Susana; González-Vallinas, Margarita; Martín-Hernández, Roberto; Sánchez-Martínez, Ruth; Dávalos Herrera, Alberto; González-Sarrías, Antonio ; Espín de Gea, Juan Carlos ; Tomás Barberán, Francisco ; Reglero, Guillermo
Issue Date2015
PublisherAmerican Society for Pharmacology and Experimental Therapeutics
CitationJournal of Pharmacology and Experimental Therapeutics 353(2): 433-444 (2015)
AbstractEllagic 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.
Identifiersdoi: 10.1124/jpet.114.221796
e-issn: 1521-0103
issn: 0022-3565
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