Crambene induces pancreatic acinar cell apoptosis via the activation of mitochondrial pathway.

Abstract

We investigated the apoptotic pathway activated by crambene (1-cyano-2-hydroxy-3-butene), a plant nitrile, on pancreatic acinar cells. As evidenced by annexin V-FITC staining, crambene treatment for 3 h induced the apoptosis but not necrosis of pancreatic acini. Caspase-3, -8, and -9 activities in acini treated with crambene were significantly higher than in untreated acini. Treatment with caspase-3, -8, and -9 inhibitors inhibited annexin V staining, as well as caspase-3 activity, pointing to an important role of these caspases in crambene-induced acinar cell apoptosis. The mitochondrial membrane potential was collapsed, and cytochrome c was released from the mitochondria in crambene-treated acini. Neither TNF-alpha nor Fas ligand levels were changed in pancreatic acinar cells after crambene treatment. These results provide evidence for the induction of pancreatic acinar cell apoptosis in vitro by crambene and suggest the involvement of mitochondrial pathway in pancreatic acinar cell apoptosis.

• Authors: Yang Cao, Sharmila Adhikari, Abel Damien Ang, Marie Véronique Clément, Matthew Wallig, Madhav Bhatia
• Journal: American journal of physiology. Gastrointestinal and liver physiology (Am J Physiol Gastrointest Liver Physiol) Vol. 291 Issue 1 Pg. G95-G101 (Jul 2006) ISSN: 0193-1857 [Print] United States
• PMID: 16603484 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alkenes
• Nitriles
• 1-cyano-2-hydroxy-3-butene
• Caspases

Topics

• Alkenes (administration & dosage)
• Animals
• Apoptosis (drug effects, physiology)
• Caspases (metabolism)
• Cell Respiration (drug effects, physiology)
• Cells, Cultured
• Dose-Response Relationship, Drug
• Enzyme Activation (drug effects)
• Male
• Membrane Potentials (drug effects, physiology)
• Mice
• Mitochondria (drug effects, physiology)
• Nitriles (administration & dosage)
• Pancreas (drug effects, metabolism)
• Signal Transduction (drug effects, physiology)