Glibenclamide exerts an antitumor activity through reactive oxygen species-c-jun NH2-terminal kinase pathway in human gastric cancer cell line MGC-803

Biochem Pharmacol. 2008 Dec 15;76(12):1705-15. doi: 10.1016/j.bcp.2008.09.009. Epub 2008 Sep 17.


Glibenclamide, a blocker of ATP-sensitive potassium (K(ATP)) channels, can suppress progression of many cancers, but the involved mechanism is unclear. Herein we reported that MGC-803 cells expressed the K(ATP) channels composed of Kir6.2 and SUR1 subunits. Glibenclamide induced cellular viability decline, coupled with cell apoptosis and reactive oxygen species (ROS) generation in MGC-803 cells. Meanwhile, glibenclamide increased NADPH oxidase catalytic subunit gp91(phox) expression and superoxide anion (O2-) generation, and caused mitochondrial respiration dysfunction in MGC-803 cells, suggesting that glibenclamide induced an increase of ROS derived from NADPH oxidase and mitochondria. Glibenclamide could also lead to loss of mitochondrial membrane potential, release of cytochrome c and apoptosis-inducing factor (AIF), and activation of c-jun NH2-terminal kinase (JNK) in MGC-803 cells. Pretreatment with antioxidant N-acetyl-l-cysteine (NAC) prevented glibenclamide-induced JNK activation, apoptosis and cellular viability decline. Furthermore, glibenclamide greatly decreased the cellular viability, induced apoptosis and inhibited Akt activation in wild-type mouse embryonic fibroblast (MEF) cells but not in JNK1-/- or JNK2-/- MEF cells. Taken together, our study reveals that glibenclamide exerts an antitumor activity in MGC-803 cells by activating ROS-dependent, JNK-driven cell apoptosis. These findings provide insights into the use of glibenclamide in the treatment of human gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cells, Cultured
  • Glyburide / pharmacology*
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Mice
  • Mitochondria / metabolism
  • Potassium Channel Blockers / pharmacology
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction / drug effects*
  • Stomach Neoplasms


  • Antineoplastic Agents
  • Potassium Channel Blockers
  • Reactive Oxygen Species
  • JNK Mitogen-Activated Protein Kinases
  • Glyburide