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Cytotoxic effects of ellagitannins isolated from walnuts in human cancer cells
Vy Le1, Debora Esposito, Mary H Grace
1a Department of Biological Sciences , San José State University , San Jose , California , USA.
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.
Insights
Walnut extract, rich in ellagitannins like Tellimagrandin I and II, shows anticancer properties by inducing apoptosis and impairing mitochondrial function in cancer cells.
Area of Science:
- Nutritional biochemistry
- Cancer biology
- Cellular mechanisms
Background:
- Walnuts possess bioactive compounds with potential anticancer properties.
- Previous studies indicated walnut diets reduce tumor size in mice.
- The precise anticancer mechanisms of walnuts remained undetermined.
Purpose of the Study:
- To investigate the anticancer effects of a walnut methanol extract on human cancer cell lines.
- To identify specific compounds responsible for the observed cytotoxicity.
- To elucidate the cellular mechanisms underlying walnut-induced cancer cell death.
Main Methods:
- Preparation and application of a methanol extract from walnuts.
- Cytotoxicity assays on MDA-MB-231, MCF7, and HeLa human cancer cells.
- Identification of bioactive compounds using chemical analysis.
- Assessment of cellular effects including intracellular pH, mitochondrial membrane potential, cytochrome c release, and mitochondrial respiration.
Main Results:
- The walnut extract exhibited cytotoxicity against all tested cancer cell lines.
- Tellimagrandin I and Tellimagrandin II were identified as major cytotoxic compounds.
- Extract treatment led to decreased intracellular pH and mitochondrial membrane depolarization.
- Cytochrome c release, phosphatidylserine flipping, and reduced mitochondrial respiration were observed.
Conclusions:
- Walnut extract induces apoptosis and impairs mitochondrial function in cancer cells.
- Ellagitannins, specifically Tellimagrandin I and II, are key mediators of these effects.
- These findings suggest a mechanism for the anticancer potential of walnuts.
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