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Food and Chemical Toxicology 43 (2005) 1557–1566 /locate/foodchemtox E ects of anthocyanidin on the inhibition of proliferation and induction of apoptosis in human gastric adenocarcinoma cells Ping-Hsiao Shih, Chi-Tai Yeh, Gow-Chin Yen * Department of Food Science, National Chung Hsing University, 250 Kuokuang Road, Taichung 40227, Taiwan Received 15 December 2004; accepted 4 May 2005 Abstract Anthocyanins are naturally occurring reddish pigments that abundant in fruits and vegetables. To investigate the mechanistic basis for the anti-tumor properties of anthocyanins, five aglycone (cyanidin, delphinidin, malvidin, pelargonidin, and peonidin) and four glycosylated (cyaniding-3-glucoside, malvidin-3-glucoside, pelargonidin-3-glucoside and peonidin-3-glucoside) anthocyanins were used to examine their e ects on cell cycle progression and induction of apoptosis in human gastric adenocarcinoma AGS cells. The data from cell viability assay showed that malvidin exhibited the most potent anti-proliferation e ect on AGS cells in a time-and dose-dependent manner (P 0.05). This event is accompanied the arrest of AGS cells at the G0/G1 phase by malvidin at the tested concentrations of 0–200 lM. Cellular uptake of anthocyanin and anthocyanidin was confirmed by HPLC analysis and the intracellular accumulation of malvidin (24.9 ± 1.1 lM/mg protein) was observed when treatment of AGS cells with malvidin for 12 h. In addition, an accumulation of AGS cells in sub-G1 phase (20% and 30% increase for 100 and 200 lM of malvidin, respectively) was observed as well as by the appearance of a fraction of cells with an aneudiploid DNA content. The occurrence of apoptosis induced by malvidin was confirmed by morphological and biochemical features, including apoptotic bodies formation, caspase-3 acti-vation and poly(ADP-ribose) polymerase proteolysis. Furthermore, the mitochondrial membrane potential of apoptotic cells after treatment with malvidin was significantly lost and resulted in the e