Induction of growth inhibition, altered ploidy, apoptosis and differentiation by anthocyanin-enriched fruit extracts and plant phenolics in leukemic and colon cancer cells

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA 5536 Our earlier studies have revealed growth inhibitory and differentiating effects of extracts from anthocyanin-enriched fruits on leukemic and colon cancer cells. An objective of the present study was to determine if these effects were specific to anthocyanins or to other polyphenolics in fractions of the fruit extracts. Methanolic extracts of peach (BY00P6653) and plum (Black Splendor) were fractionated using a C18 cartridge. Phenolic and anthocyanin fractions were eluted with ethyl acetate and methanol containing 5% formic acid. When DS19 mouse erythroleukemic cells were treated with either phenolic or anthocyanin fractions, the percentage of tetraploid cells increased as compared to the controls and there was an increased occurrence of apoptosis. The induction of tetraploidy with increased concentration of phenolics was biphasic with a decrease at high concentrations. Inhibition of cell proliferation of the DS19 mouse erythroleukemia cells was also observed. A decrease in the diploid S phase and an increase in the diploid G1 phase further illustrated the inhibition of cell proliferation. With an increase in phenolics or anthocyanin concentration we observed a decrease in cell growth. Chlorogenic acid is a major plant phenolic acid. It was observed that with an increase in chlorogenic acid concentration the percentage of tetraploid DS19 cells increased as did the percentage of apoptotic cells. Cell proliferation of the DS19 erythroleukemia cells was also inhibited by the addition of chlorogenic acid suggesting that this component of the phenolics fraction may be an important contributor to the actions on erythroleukemia cells. In Caco-2 human colon cancer cells the anthocyanin fraction but not the phenolic fraction caused the induction of differentiation as judged by increased alkaline phosphatase activity. The inhibition of growth by anthocyanin fractions and individual plant phenolics (chlorogenic acid, protocatechuic acid and caffeic acid) was enhanced by coincubation with the anti-oxidant, ascorbic acid, but there was little additional effect by coincubation of phenolic compounds with another antioxidant compound, N-acetylcysteine. It was concluded that several plant phenolic molecules can influence growth, differentiation and cell cycle parameters of cancer cells.