Gallic acid as a cancer-selective agent induces apoptosis in pancreatic cancer cells

Chemotherapy. 2012;58(3):185-94. doi: 10.1159/000337103. Epub 2012 Jun 22.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Caspase 9 / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Gallic Acid / pharmacology*
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Reactive Oxygen Species / metabolism
  • bcl-2-Associated X Protein / metabolism


  • Reactive Oxygen Species
  • bcl-2-Associated X Protein
  • Gallic Acid
  • Caspase 3
  • Caspase 9