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.

Additional information

Funding

This work was funded by grants from the California Walnut Commission (Joseph Brandon White and Mary Ann Lila). The California Walnut Commission did not have input into experimental design or the interpretation or reporting of the findings. Joseph Brandon White and Mary Ann Lila were the principle investigators on the grants, designed the experiments, interpreted the results, and prepared this report. John Kim, Roy Okuda, and Mary H. Grace prepared the walnut extracts as described. Anh Pham, Anthony Bortolazzo, Debora Esposito, and Vy Le carried out the various experiments as described. DE and Slavko Komarnytsky designed, performed, and summarized mitochondrial bioenergetics studies using Seahorse XF24 assay platform.