Ellagic Acid, a Dietary Polyphenol, Selectively Cytotoxic to HSC-2 Oral Carcinoma Cells

The antiproliferative and apoptotic effects of ellagic acid, a dietary polyphenol, were studied. 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. 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). Ellagic acid exhibited significant antioxidant, but not pro-oxidant, activity and was selectively cytotoxic to oral carcinoma cells.