title: Cytotoxic effects of ellagitannins isolated from walnuts in human cancer cells.
abstract: Walnuts contain many bioactive components that may slow cancer growth. A previous report showed that a diet supplemented with walnuts decreased the tumor size formed by MDA-MB-231 human cancer cells injected into nude mice. However, the mechanism of action was never determined. We characterized the effects of a methanol extract prepared from walnuts on human MDA-MB-231, MCF7, and HeLa cells. The extract was cytotoxic to all cancer cells. We identified compounds from the methanol extract that induced this cytotoxicity. The predominant compounds were Tellimagrandin I and Tellimagrandin II, members of the ellagitannin family. We also show a walnut extract decreases the intracellular pH, depolarizes the mitochondrial membrane with release of cytochrome c and phosphatidylserine flipping. The antimitogenic effects of walnut extract were associated with a twofold reduction of mitochondria respiration. These results suggest impairment of mitochondrial function and apoptosis as relevant mechanism of anticancer effects of the walnut extract.
authors.affiliation: a Department of Biological Sciences , San José State University , San Jose , California , USA.
authors.forename: Vy
authors.initials: V
authors.lastname: Le
authors.forename: Debora
authors.initials: D
authors.lastname: Esposito
authors.forename: Mary H
authors.initials: MH
authors.lastname: Grace
authors.forename: Danny
authors.initials: D
authors.lastname: Ha
authors.forename: Anh
authors.initials: A
authors.lastname: Pham
authors.forename: Anthony
authors.initials: A
authors.lastname: Bortolazzo
authors.forename: Zackery
authors.initials: Z
authors.lastname: Bevens
authors.forename: John
authors.initials: J
authors.lastname: Kim
authors.forename: Roy
authors.initials: R
authors.lastname: Okuda
authors.forename: Slavko
authors.initials: S
authors.lastname: Komarnytsky
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Lila
authors.forename: Joseph Brandon
authors.initials: JB
authors.lastname: White
mesh_terms: D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D056744:Cyclin B1 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004032:Diet; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D031324:Juglans / Q000737:chemistry*; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D008928:Mitochondria / Q000187:drug effects; D009754:Nuts / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology
chemical_list: D056744:Cyclin B1; D047348:Hydrolyzable Tannins; D010936:Plant Extracts; C013515:ellagitannin; D045304:Cytochromes c