Gallic acid as a cancer-selective agent induces apoptosis in pancreatic cancer cells.
BACKGROUND
Gallic acid (GA) is a plant phenol isolated from water caltrop which is reported to have anti-inflammatory and anti-cancer effects. In this study, the antiproliferative effect of GA on human pancreatic cancer cell lines CFPAC-1 and MiaPaCa-2 as well as hepatocytes HL-7702 as normal cells was examined. Particularly, the mechanism of GA-induced apoptosis in MiaPaCa-2 cells in vitro was further studied.


METHODS
Cell viability was measured using SRB assay, and apoptosis was detected by Hoechst staining and annexin V-PI staining assays. Mitochondrial membrane potential was detected by rhodamine-123 staining. Flow cytometry analysis was employed to detect the apoptosis-related events.


RESULTS
GA inhibited the proliferation of CFPAC-1 and MiaPaCa-2 cells in a time- and dose-dependent manner, with IC(50)S of 102.3 ± 2.4 and 135.2 ± 0.6 µM at 48 h, respectively. GA treatment led to the increased proportion of cell apoptosis from 12.5 ± 0.72 to 78.3 ± 2.48% at the concentrations of 6.25 and 25.0 µg/ml, which was evidenced again by chromatins staining assay. Also, GA activated caspase-3, caspase-9, and reactive oxygen species, elevated Bax expression and [Ca(2+)](i) and reduced mitochondrial membrane potential (ΔΨm) in MiaPaCa-2 cells. Remarkably, when compared with human normal cells HL-7702 (IC(50) >100 µg/ml), GA showed selective toxicity for cancer cells.


CONCLUSIONS
GA can function as a cancer-selective agent by inducing apoptosis in MiaPaCa-2 cells via the mitochondria-mediated pathways. To the best of our knowledge, GA should open up new opportunities for the therapy of pancreatic cancer.
School of Public Health, Jilin University, Changchun, PR China.
Zuojia
Z
Liu
Dan
D
Li
Lijun
L
Yu
Fenglan
F
Niu
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005707:Gallic Acid / Q000494:pharmacology*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D005707:Gallic Acid; D053148:Caspase 3; D053453:Caspase 9