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© 2003 The American Society for Nutritional Sciences J. Nutr. 133:2669-2674, August 2003


Nutrition and Cancer

Low Concentrations of Quercetin and Ellagic Acid Synergistically Influence Proliferation, Cytotoxicity and Apoptosis in MOLT-4 Human Leukemia Cells–

Susanne U. Mertens-Talcott, Stephen T. Talcott and Susan S. Percival4

Food Science and Human Nutrition Department, University of Florida, Gainesville, FL 32611

4To whom correspondence should be addressed. E-mail: percival{at}ufl.edu.

Little information is available regarding possible synergistic or antagonistic biochemical interactions among polyphenols contained in fruits and vegetables. Identifying potential interactions among these compounds may help to define the efficiency of polyphenol-containing foods in cancer prevention as related to structure-function activity of the compounds. The objective of this study was to investigate interactions between quercetin and ellagic acid, two polyphenolics that are present predominantly in small fruits, on cell death and proliferation-related variables in the MOLT-4 human leukemia cell line. Assays were performed to determine cell cycle kinetics, proliferation, apoptotic DNA-fragmentation and caspase-3-activity after 12, 24 and 48 h. Ellagic acid significantly potentiated the effects of quercetin (at 5 and 10 µmol/L each) in the reduction of proliferation and viability and the induction of apoptosis. Significant alterations in cell cycle kinetics were also observed. The synergy was confirmed by an isobolographic analysis of the cell proliferation data. The interaction of ellagic acid and quercetin demonstrated an enhanced anticarcinogenic potential of polyphenol combinations, which was not based solely on the additive effect of individual compounds, but rather on synergistic biochemical interactions.


KEY WORDS: • phytochemicals • polyphenols • anticancer • apoptosis • potentiation




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