Title: Induction of apoptosis in acute lymphoblastic leukemia cells by isolated fractions from strawberries Authors
Submitted to: Journal of Functional Foods
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: January 6, 2009
Publication Date: February 28, 2009
Citation: Zunino, S.J., Seerum, N.P., Zhang, Y., Storms, D.H. 2009. Induction of apoptosis in acute lymphoblastic leukemia cells by isolated fractions from strawberries. Journal of Agricultural and Food Chemistry, 1(2), pp. 153-160. Interpretive Summary: Strawberries contain chemicals with anti-cancer activity. We isolated different chemicals from strawberries and tested whether these constituents where able to kill acute leukemia cells derived from patients with acute lymphoblastic leukemia. The strawberry powder used to isolate the chemicals was prepared by the California Strawberry Commission and contained a mixture of commonly and currently used cultivars. Three measures of cell death (apoptosis) were performed after treating these cells for 72 hours with multiple doses of isolated chemicals. The cells were tested for depolarization of mitochondrial membranes, activation of caspase-3, a downstream enzyme in the apoptotic pathway, and for loss of nuclear DNA which occurs at late stages of apoptosis. Several chemicals isolated from strawberries showed a significant ability to kill the leukemia cells, including the flavanoids quercetin, kaempferol, and a mixture of ellagitannins. These data show that constituents of strawberries are able to induce apoptosis in leukemia cells and may have potential in the treatment or prevention of this disease.
Technical Abstract: Strawberries contain phytochemicals that have anti-inflammatory and anti-cancer activity. We investigated the ability of isolated fractions from strawberry extracts to induce apoptotic cell death in three pre-B acute lymphoblastic leukemia (ALL) lines, including SEM and RS4;11 cell lines derived from patients with high-risk B-ALL carrying the t(4;11)(q21;q23) chromosomal translocation and REH cells without the translocation. Strawberry powder containing a mixture of California cultivars was extracted A 24 h screening for mitochondrial membrane depolarization using the dye JC-1 was first performed to evaluate fractions with potential anti-cancer activity. Cells were treated every 24 h with fresh medium containing aliquots of each strawberry fraction for a total of 72 h. Apoptosis was characterized by depolarization of mitochondrial membranes, activation of caspase-3, and loss of nuclear. Fractions containing the purified flavanoids quercetin and kaempferol induced significant apoptosis in all three lines. The t(4;11) lines SEM and RS4;11 were not sensitive to the strawberry fraction containing a mixture of ellagitannins; however, REH cells showed approximately 25% cell death when treated with multiple doses of this preparation. These data show that constituents of strawberries are able to induce apoptosis in high-risk leukemia cells and may have potential in the treatment or prevention of this disease.