Study on effect and mechanism of ellagic acid on the proliferation and apoptosis of pancreatic cancer cell line PANC-1

Objective To investigate the effect of ellagic acid on the proliferation and apoptosis of pancreatic cell line PANC-1 in vitro and explore possible mechanism of ellagic acid's effect on PANC-1 cells. Methods PANC-1 cells were treated with ellagic acid at concentrations of 0, 2, 4, 6, 8 μg/ml for 24, 48 and 72 h respectively. Inverted Microscope showed cells' morphological changes. The cell proliferation was determined by methyl thiazolyl tetrazolium (MTT) assay. When the cells were treated with ellagic acid at concentrations of 0, 2, 4, 6 μg/ml for 48 h, the morphological changes of apoptotic cells were observed by cell staining, apoptotic rate and cell cycle were detected by flow cytometry, the protein expression of cyclo-oxgenase 2 (COX-2) and nuclear factor-κB (NF-κB) were measured by Western blotting. Results Ellagic acid could significantly inhibited the growth of PANC-1 cells in a concentration-dependent and time-dependent manner. The difference among these groups were statistically significant(P<0.05). After treatment with ellagic acid, apoptosis of PANC-1 cells was seen. Apoptosis rates in the different concentration groups were respectively (11.18±0.99)%, (20.70±2.32)%, (39.68±0.69)%, the apoptosis rate of control group [(0.62±0.23)%] compared with statistically significant difference among the different concentration groups (P<0.05). The percentages of G0/G1 phase cells were respectively(48.98±2.36)%, (60.80±1.40)%, (72.82±0.59)%, the percentage of control group [(42.78±0.74)%] compared with statistically significant difference among the different concentration groups(P<0.05). The protein expression of COX-2 and NF-κB measured by Western blotting were significantly down-regulated dose-dependently. Conclusion Ellagic acid can inhibit the proliferation of pancreatic cancer cell line PANC-1 and induce apoptosis. The mechanism may depend on arresting cell cycle and decreasing protein expression of COX-2 and NF-κB. Key words: Ellagic acid; Pancreatic neoplasm; Proliferation; Apoptosis; Cyclo-oxgenase 2; Nuclear factor-κB