ABSTRACT
BACKGROUND: The antiproliferative and apoptotic effects of ellagic acid, a dietary polyphenol, were studied. MATERIALS AND METHODS: The neutral red cytotoxicity assay compared the sensitivities of gingival fibroblasts and HSC-2 oral carcinoma cells to ellagic acid. The ferrous ion oxidation xylenol orange assay and levels of intracellular reduced glutathione were used to assess pro-oxidant nature of ellagic acid. Antioxidant activity was demonstrated in cells co-treated with H2O2 and ellagic acid by 2',7'-dichlorodihydrofluorescein diacetate staining and in cells co-treated with gallic acid and ellagic acid by morphological analysis. Apoptosis was assessed by microscopy, flow cytometry, luminescence, and immunoblotting. RESULTS: Ellagic acid was cytotoxic to carcinoma cells, but not to normal cells. Its pro-oxidant nature was minimal, whereas its antioxidant property was biologically significant. Ellagic acid-treated cells demonstrated apoptotic morphology, induction of apoptosis (flow cytometry), increase in caspase 3/7 activities (luminescence), and activation of caspase 3 and cleavage of poly ADP ribose polymerase (immunoblot). CONCLUSION: Ellagic acid exhibited significant antioxidant, but not pro-oxidant, activity and was selectively cytotoxic to oral carcinoma cells.
