Gallic Acid as a Cancer-Selective Agent Induces Apoptosis in Pancreatic Cancer Cells

• Published in: Chemotherapy (Basel) Vol. 58; no. 3; pp. 185 - 194
• Main Authors: Liu, Zuojia, Li, Dan, Yu, Lijun, Niu, Fenglan
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2012
• Subjects: Apoptosis; Apoptosis - drug effects; bcl-2-Associated X Protein - metabolism; Caspase 3 - metabolism; Caspase 9 - metabolism; Cell Line, Tumor; Cell Survival - drug effects; Experimental Chemotherapy; Gallic Acid - pharmacology; Humans; Membrane Potential, Mitochondrial - drug effects; Pancreatic cancer; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; Polyphenols; Reactive Oxygen Species - metabolism; Mitochondrial pathway; Gallic acid; Pancreatic cancer; Plant polyphenol; Apoptosis
• ISSN: 0009-3157; 1421-9794
• DOI: 10.1159/000337103

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.