Submitted on November 6, 2005
Accepted on March 16, 2006
Crambene induces pancreatic acinar cell apoptosis via the activation of mitochondrial pathway
Yang Cao1, Sharmila Adhikari1, Abel D Ang1, Marie V Clement1, Matthew Wallig1, and Madhav Bhatia1*
1 Pharmacology, National University of Singapore, Singapore, Singapore; Biochemistry, National University of Singapore, Singapore, Singapore; Pathobiology, University of Illinois at Urbana Champaign, Urbana, Illinois, United States
* To whom correspondence should be addressed. E-mail: mbhatia{at}nus.edu.sg.
We investigated the apoptotic pathway activated by crambene (1-cyano-2-hydroxy-3-butene-CHB), a plant nitrile, on pancreatic acinar cells. As evidenced by annexin V-FITC staining, crambene treatment for 3 hours induced the apoptosis but not necrosis of pancreatic acini. Caspase 3, 8 and 9 activity 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 mitochondria membrane potential was collapsed and cytochrome C released from the mitochondria in crambene-treated acini. Neither TNF-
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.
