Crambene induces pancreatic acinar cell apoptosis via the activation of mitochondrial pathway.
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.
Cao
Yang
Y
Department of Pharmacology, National University of Singapore, Yong Loo Lin School of Medicine, Singapore 117597.
Adhikari
Sharmila
S
Ang
Abel Damien
AD
Clément
Marie Véronique
MV
Wallig
Matthew
M
Bhatia
Madhav
M
D000475:Alkenes / Q000008:administration & dosage*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D020169:Caspases / Q000378:metabolism*; D019069:Cell Respiration / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D009570:Nitriles / Q000008:administration & dosage*; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D000475:Alkenes; D009570:Nitriles; C055903:1-cyano-2-hydroxy-3-butene; D020169:Caspases